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118 Study Matches
MT2013-09C : Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases
This is a treatment protocol for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. There is no research element except the collection of routine clinical data.
Margaret MacMillan, MD
All
up to 55 Years old
N/A
NCT01962636
1305M34181
Inclusion Criteria:
• Eligible Disease Status
• Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
• Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
• Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
• Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
• Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
• Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
• Advanced Myelofibrosis
• Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10% by a representative bone marrow aspirate morphology.
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
• Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
• Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
• Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
• Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
• Myeloproliferative Syndromes
• Availability of suitable UCB unit(s)
• 0 to 55 years
• Voluntary written consent (adult or parental/guardian)
Exclusion Criteria:
• previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
• chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens)
• if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
• extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
• pregnant or breastfeeding
• HIV positive
Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total Body Irradiation, Drug: Cyclosporine A, Drug: Mycophenylate mofetil, Biological: Umbilical cord blood
Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myelofibrosis, Myelodysplasia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Lymphoblastic Lymphoma, Burkitt's Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma
Umbilical Cord Transplant, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myelofibrosis, Myelodysplasia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Large Cell Non-Hodgkin Lymphoma, Lymphoblastic Lymphoma, Burkitt's Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, Clinics and Surgery Center (CSC)
COG ANBL00B1 - Neuroblastoma Biology Studies
This research trial studies biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglio-neuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.
Emily Greengard
All
up to 30 Years old
N/A
NCT00904241
0807M39682
Inclusion Criteria:
• All newly diagnosed patients with suspected neuroblastoma, suspected ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype seen at Children's Oncology Group (COG) institutions are eligible for this study
• There will be no penalty under any circumstances for enrollment of a patient whose definitive institutional diagnosis, or central review diagnosis, is found to be a tumor other than neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/ maturing subtype
• Patients may not have received chemotherapy prior to enrollment on ANBL00B1 and procurement of study-related tissues with the following exception:
• Patients that in the opinion of the treating physician are too ill to undergo pre-treatment tissue biopsy and require EMERGENT chemotherapy may be enrolled on ANBL00B1; documentation of the emergent nature of therapy initiation is required
• It is required that a good faith effort (documented by specimen tracking) be made to submit a neuroblastoma sample (tumor, metastasis, and/or tumor-involved bone marrow) of sufficient quality for MYCN analysis in the Neuroblastoma Reference Laboratory in order for any newly diagnosed patient to be enrolled on ANBL00B1; this should be obtained prior to initiation of therapy
• Exceptions
• In rare cases, patients may be deemed too ill to undergo pre-treatment tissue biopsy and require EMERGENT therapy; the following eligibility guidelines apply to these cases:
• For presumed INSS stage 4S patients: Efforts to submit tumor tissue (e.g., primary tumor, skin nodule, or metastatic site) within 96 hours of EMERGENT therapy initiation should be made; however, if the child is deemed too unstable for such a procedure they may still be enrolled as long as pre-treatment peripheral blood and serum have been submitted
• For all other INSS stages: tumor tissue should be obtained as soon as possible within 96 hours of EMERGENT therapy initiation; patients without tumor tissues submitted within this time-frame are not eligible for enrollment
• Note: it may not be possible to obtain all necessary tumor biomarkers for therapy stratification in such cases; if a patient enrolled on ANBL00B1 undergoes an additional diagnostic procedure within 96 hours of initiating therapy, additional tumor specimens may be submitted to obtain biomarkers used for risk classification; the decision to perform such procedures, and/or submit these specimens, is to be made by the managing clinicians and should reflect the clinical need to know the status of such biomarkers
• Patients enrolled on ANBL1232 in Group A (either A1 or A2) will not have a tumor biopsy or resection upfront; tumor tissue submission is therefore not required for these patients to enroll on ANBL00B1; a peripheral blood and serum sample is the only specimen required to be submitted for this group of patients; should they undergo a biopsy or resection at a later date tumor can be submitted for biomarker testing at this time
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original diagnosis are NOT eligible; samples should be submitted as part of the ABTR04B1 protocol
Other: Cytology Specimen Collection Procedure, Other: Laboratory Biomarker Analysis
Ganglioneuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Regional Neuroblastoma, Stage 4 Neuroblastoma, Stage 4S Neuroblastoma
COG AREN03B2: Renal Tumors Classification, Biology and Banking Study.
• To classify patients (< 30 years old) with renal tumors by histological categorization, surgico-pathological stage, presence of metastases, age at diagnosis, tumor weight and loss of heterozygosity for chromosomes 1p and 16q, to thereby define eligibility for a series of therapeutic studies. • To maintain a biological samples bank to make specimens available to scientists to evaluate additional potential biological prognostic variables and for the conduct of other research by scientists.
Emily Greengard
All
up to 29 Years old
N/A
NCT00898365
0708M15261
Inclusion Criteria:
• Patients with the first occurrence of any tumor of the kidney identified on CT scan or MRI are eligible for this study; histologic diagnosis is not required prior to enrollment but is required for all patients once on study
• Eligible tumors include (but are not limited to):
• Nephroblastic tumors
• Nephroblastoma (Wilms' tumor) (favorable histology, anaplasia [diffuse, focal])
• Nephrogenic rests and nephroblastomatosis
• Cystic nephroma and cystic partially differentiated nephroblastoma
• Metanephric tumors (metanephric adenoma, metanephric adenofibroma, metanephric stromal tumor)
• Mesoblastic nephroma (cellular, classic, mixed)
• Clear cell sarcoma
• Rhabdoid tumor (any malignant rhabdoid tumor occurring outside the central nervous system [CNS])
• Renal epithelioid tumors of childhood (papillary renal cell carcinoma, medullary renal cell carcinoma, renal tumors associated with Xp11.2 translocations, oncocytic renal neoplasms after neuroblastoma)
• Angiolipoma
• Ossifying renal tumor of infancy
• Patients with the first occurrence of the following tumors are also eligible:
• Extrarenal nephroblastoma or extrarenal neprogenic rests
• Malignant rhabdoid tumor occurring anywhere outside the central nervous system
• Required specimens, reports, forms, and copies of imaging studies must be available or will become available for submission and the institution must intend on submitting them as described in the protocol procedures
• For ALL patients, (with exception of bilateral, bilaterally predisposed, multicentric, or unilateral tumor in solitary kidney planning to enroll without biopsy***), the following submissions are required:
• A complete set of recut hematoxylin and eosin (H & E) slides (including from sampled lymph nodes, if patient had upfront nephrectomy)
• * Tissue must be from diagnosis, prior to any renal tumor directed chemotherapy or radiation (only exception is for presumed favorable histology Wilms tumor [FHWT] patients discovered to have diffuse anaplastic Wilms tumor [DAWT] at delayed nephrectomy and plan to enroll at delayed nephrectomy)
• Representative formalin-fixed paraffin-embedded tissue block or if a block is unavailable, 10 unstained slides from a representative block of tumor, if available.
• Tissue must be from diagnosis, prior to any renal tumor directed chemotherapy or radiation (only exception is for presumed FHWT patients discovered to have DAWT at delayed nephrectomy and plan to enroll at delayed nephrectomy)
• Institutional pathology report, Specimen Transmittal Form, and Pre-Treatment Pathology Checklist
• Copies of images and institutional reports of CT and/or MRI abdomen and pelvis, and Pre Treatment Imaging Checklist
• Copies of images and institutional report of chest CT for all malignant tumors
• Institutional surgical report(s) and Pre-Treatment Surgical Checklist
• CRFs: Staging Checklist and Metastatic Disease Form (if metastatic disease is noted on imaging)
• Patients with bilateral, bilaterally predisposed, multicentric, or unilateral tumor in solitary kidney planning to enroll without biopsy via imaging only - these patients will not have central review or have a risk assignment issued, but may contribute to specimen banking for future research. However, if biopsy is done, tissue must be submitted as for other renal tumors, and initial risk assignment will require pathology and surgical rapid central reviews. The Specimen Transmittal Form and Pre Treatment Pathology Checklist are also needed.
• Please note: if the above required items are not received within 120 days of study enrollment, the patient will be considered off study
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Other: Cytology Specimen Collection Procedure, Other: Laboratory Biomarker Analysis
Adult Cystic Nephroma, Anaplastic Kidney Wilms Tumor, Angiolipoma, Cellular Congenital Mesoblastic Nephroma, Classic Congenital Mesoblastic Nephroma, Clear Cell Sarcoma of the Kidney, Congenital Mesoblastic Nephroma, Cystic Partially Differentiated Kidney Nephroblastoma, Diffuse Hyperplastic Perilobar Nephroblastomatosis, Extrarenal Rhabdoid Tumor, Kidney Medullary Carcinoma, Kidney Neoplasm, Kidney Oncocytoma, Kidney Wilms Tumor, Metanephric Adenofibroma, Metanephric Adenoma, Metanephric Stromal Tumor, Metanephric Tumor, Mixed Congenital Mesoblastic Nephroma, Ossifying Renal Tumor of Infancy, Papillary Renal Cell Carcinoma, Renal Cell Carcinoma, Renal Cell Carcinoma Associated With Xp11.2 Translocations/TFE3 Gene Fusions, Rhabdoid Tumor of the Kidney, Wilms Tumor
MT2011-09C Alkylator-Intense Conditioning Followed By Autologous Transplantation for Patients with High Risk or Relapsed Solid or CNS Tumors
Treatment guidelines for high risk or relapsed solid tumors consisting of a busulfan, melphalan, thiotepa conditioning followed by an autologous peripheral blood stem cell transplant and, if appropriate, disease specific radiation therapy at day 60+
Ashish Gupta
All
up to 70 Years old
N/A
NCT01505569
1107M02641
Inclusion Criteria:
All patients must have histological verification of malignancy at original diagnosis.
• Eligible Diseases
• Arm A: Solid Tumor
• Ewing's Family Tumors (ES/PNET/DSRCT) - metastatic at time of diagnosis and/or relapsed after therapy
• Renal Tumors - relapsed (all histology - Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor)
• Hepatoblastoma - metastatic at time of diagnosis and/or relapsed after therapy
• Rhabdomyosarcoma - metastatic at time of diagnosis and/or relapsed after therapy
• Soft Tissue Sarcoma - chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
• Primary Malignant Brain Neoplasms <18 years of age - at diagnosis and/or relapse
• Retinoblastoma - disseminated at diagnosis and/or relapsed
• CNS Lymphoma - primary or secondary CNS lymphoma.
• Other High Risk Metastatic or Relapsed Solid Tumors - to be approved by 2 or more pediatric hematology/oncology and bone marrow transplant (BMT) physicians
• Arm B: Certain CNS tumors
• Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
• > 1.5 cm2 residual disease following resection for any Medulloblastoma histology
• lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
• MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
• Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
• Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
• Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
• Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
• Other High Risk CNS Tumors - to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
• Arm C: Germ Cell Tumors
• Confirmation of germ cell tumor (GCT) histology (both seminoma and nonseminoma). Tumor may have originated in any primary site. NOTE: In rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established. This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG ≥ 500; AFP ≥ 500} and typical pattern of metastases).
• One or more unfavorable prognostic features for achieving a CR with conventional-dose chemotherapy. Unfavorable prognostic features include:
• extragonadal primary site
• PD following an incomplete response (IR) to first-line therapy,
• PD after a conventional-dose salvage (cisplatin + ifosfamide -based) regimen
• Arm D: Certain CNS Tumor patients who can only undergo one transplant
• Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
• > 1.5 cm2 residual disease following resection for any Medulloblastoma histology
• lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
• MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
• Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
• Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
• Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
• Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
• Other High Risk CNS Tumors including choroid plexus carcinoma in children- to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
• Arm E: Neuroblastoma ** Neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites.
• Disease Status at Enrollment
• Arm A, Arm B and Arm D must have fit one of the following:
• no evidence of disease or
• stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or CT and/or MRI) within 4 weeks of study entry
• Arm C: Evidence of progressive or recurrent GCT (measurable or non-measurable) following one or more cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:
• Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT. Patients with incomplete gross resection where viable GCT is found are considered eligible.
• Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
• Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase.
• Arm E: Patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria.
• Patients with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
• Age > 18 months (> 547 days) regardless of biologic features or
• Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown.
• Patients with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
• Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status.
• Patients with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.
• Patients with newly diagnosed neuroblastoma with INSS Stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features.
• Patients ≥ 365 days initially diagnosed with neuroblastoma INSS Stage 1, 2, 4S who progressed to aStage 4 without interval chemotherapy.
• Age and Performance Status
• Age and Performance Status, Arm A
• Age: 0 - 70 years
• Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Note: Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
• Age and Performance Status, Arm B
• Age: see Eligible diseases, section 3.1, for age criteria
• Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Note: Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
• Age and Performance Status, Arm C
• Age: 0-70 years of age
• Performance status: Karnofsky Performance Status ≥ 70% for patients > 16 years of age or Lansky Play Score ≥ 70 for patients ≤ 16 years of age
• Age and Performance Status, Arm D
• Age: see Eligible diseases, section 3.1, for age criteria
• Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
• Age and Performance Status, Arm E
• Age: Patients must be ≤ 30 years of age at the time of initial diagnosis.
• Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age
• Organ Function
• Organ Function, Arm A
• Hematologic: hemoglobin of >9 gm/dl and platelet count > 20,000/μl. Patients may receive transfusions as necessary.
• Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
• Hepatic: AST or ALT ≤ 5 x ULN and bilirubin ≤ 5 x ULN
• Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
• Pulmonary: oxygen saturation > 92% at rest (on room air)
• Organ Function, Arm B (to begin first consolidation cycle)
• Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
• Hematologic: ANC > 750/μl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/μl (transfusion independent).
• Renal: GFR ≥ 50 ml/min/1.73m2
• Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
• Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
• Pulmonary: oxygen saturation > 94% at rest (on room air)
• Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
• Organ Function, Arm C (to begin TI chemotherapy)
• Hematologic: ANC ≥ 750/mm3, platelets ≥ 75,000/mm3
• Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
• Hepatic: AST or ALT ≤ 2.5 x upper limits of normal (ULN), if hepatic involvement < 5 x ULN; bilirubin ≤ 2.0 x upper limits of normal (ULN)
• Arms A and C: Patients with a history of CNS tumor involvement are eligible if they have completed treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered from or stabilization of the side effects associated with the therapy and have no evidence of progressive CNS disease at the time of enrollment
• Organ Function, Arm D
• Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
• Hematologic: ANC > 750/μl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/μl (transfusion independent).
• Renal: GFR ≥ 50 ml/min/1.73m2
• Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
• Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
• Pulmonary: oxygen saturation > 92% at rest (on room air)
• Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
• Organ Function, Arm E
• No evidence of disease progression: defined as increase in tumor size of >25% or new lesions.
• Timing: Recovery from last induction course of chemotherapy.
• Minimum frozen PBSC of 4 x 106 CD34 cells/kg as 2 aliquots; i.e. 2 x 106 CD34 cells/kg for each transplant are mandatory. A third aliquot of 2 x 106 CD34 cells/kg is strongly recommended for back-up.
• Hepatic: AST < 3 x upper normal
• Cardiac: Shortening fraction ≥ 27%, or ejection fraction ≥ 50%, no clinical congestive heart failure.
• Renal: Creatinine clearance or GFR > 60 ml/min/1.73m2 (If a creatinine clearance is performed at end of induction and the result is < 100 ml/min/1.73m2, a GFR must be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m2.)
Exclusion Criteria:
• Arm A, B, C, and D:
• Pregnant or breastfeeding
• Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive constitute progressive disease.
• Concomitant enrollment on clinical study (such as COG study) that does not allow co-enrollment on this standard of care protocol (Arm B only)
• Arm E: Pregnant or breastfeeding
• Active, uncontrolled infection and/or HIV positive
• Known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
• Patients that are 12-18 months of age with INSS Stage 4 and all 3 favorable biologic features (ie, non- amplified MYCN, favorable pathology, and DNA index > 1).
Drug: Ifosfamide, Drug: Etoposide, Drug: Mesna, Biological: G-CSF, Drug: Busulfan, Drug: Melphalan, Drug: Thiotepa, Biological: Autologous stem cell infusion, Radiation: Radiation, Drug: Carboplatin, Drug: Paclitaxel, Procedure: Leukapheresis, Drug: Anti-seizure prophylaxis, Drug: Ursodiol
Ewing's Family Tumors, Renal Tumors, Hepatoblastoma, Rhabdomyosarcoma, Soft Tissue Sarcoma, Primary Malignant Brain Neoplasms, Retinoblastoma, Medulloblastoma, Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET), Atypical Teratoid/Rhabdoid Tumor (AT/RT), CNS Tumors, Germ Cell Tumors
autologous transplantation, high risk solid tumor, relapsed solid tumor, Clinics and Surgery Center (CSC)
MT2005-25 Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia
To determine the incidence of engraftment (defined as achieving donor derived neutrophil count >500/uL by day 42) in young children with leukemia or myelodysplastic syndrome undergoing a partially matched single unit umbilical cord blood transplant (UCBT) after a myeloablative preparative regimen consisting of busulfan, melphalan and fludarabine.
Christen Ebens
All
up to 3 Years old
Phase 2
NCT00357565
0511M77206
Inclusion Criteria:
• Matched sibling donor (HLA 8/8), if available, or a unrelated partially HLA matched single unit based on the following priority:
• 1st priority: 4/6 matched unit, cell dose >5 x 10-7 nucleated cells/kg
• 2nd priority: 5/6 matched unit, cell dose > 4 x 10-7 nucleated cells/kg
• 3rd priority: 6/6 matched unit, cell dose > 3 x 10-7 nucleated cells/kg
• Patients aged ≤ 3 years at diagnosis (not age of transplant) with hematological malignancy as detailed below:
• Acute myeloid leukemia: high risk CR1 as evidenced by:
• High risk cytogenetics t(4;11) or other MLL rearrangements; chromosome 5, 7, or 19 abnormalities; complex karyotype (>5 distinct changes); ≥ 2 cycles to obtain complete response (CR); CR2 or higher; Preceding myelodysplastic syndrome (MDS); All patients must be in CR or early relapse (i.e., <15% blasts in BM).
• Acute lymphocytic leukemia: high risk CR1 as evidenced by: High-risk cytogenetic: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22); >1 cycle to obtain CR; CR2 or higher; All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
• Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.
• Persistent or rising minimal residual disease (MRD) after standard chemotherapy regimens: Patients with evidence of minimal residual disease at the completion of therapy or evidence of rising MRD while on therapy. MRD will be defined by either flow cytometry (>0.1% residual cells in the blast gate with immune phenotype of original leukemic clone), by molecular techniques (PCR or FISH) or conventional cytogenetics (g-banding).
• New Leukemia Subtypes: A major effort in the field of pediatric hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new high risk features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
• Recipients must have a Lansky score ≥ 50% and have acceptable organ function defined as:
• Renal: glomerial filtration rate > 60ml/min/1.73m^2
• Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal,
• Pulmonary function: oxygen saturation >92%
• Cardiac: left ventricular ejection fraction > 45%.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
Exclusion Criteria:
• Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).
• History of HIV infection or known positive serology
• Myeloablative transplant within the last 6 months.
• Evidence of active extramedullary disease (including central nervous system leukemia).
Biological: filgrastim, Drug: busulfan, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: melphalan, Drug: mycophenolate mofetil, Procedure: umbilical cord blood transplantation
Leukemia, Myelodysplastic Syndromes, Childhood Acute Myeloid Leukemia in Remission, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Previously Treated Myelodysplastic Syndrome, Secondary Myelodysplastic Syndrome, Refractory Anemia With Excess Blasts in Transformation, Refractory Anemia With Excess Blasts, Refractory Anemia, De Novo Myelodysplastic Syndrome, Childhood Myelodysplastic Syndrome
MDS, AML
MT1999-20 Hematopoietic cell transplantation in children with juvenile myelomonocytic leukemia
To determine the probability of long-term disease-free survival in patients with JMML treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by hematopoietic cell transplantation.
Margaret MacMillan, MD
All
up to 18 Years old
Phase 1/Phase 2
NCT00167219
9911M24961
Inclusion Criteria:
• Patients must have a diagnosis of JMML and fulfill these minimal criteria (International diagnostic criteria for JMML):
• Leukocytosis (> 13,000) with absolute monocytosis (> 1,000)
• The presence of immature myeloid cells in the peripheral blood
• Less than 30% marrow blasts
• Absence of t(9:22) or BCR-ABL transcript
• Adequate major organ function including:
• Cardiac: ejection fraction > 45%
• Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
• Karnofsky performance status > 70% or Lansky score > 50%
• Creatinine must be < 2 x normal for age
• Written informed consent.
Exclusion Criteria:
• Active uncontrolled infection within one week of HCT.
Biological: Stem Cell Transplant, Drug: Preparative Regimen
Juvenile Myelomonocytic Leukemia
Stem cell transplant, long term survival, retinoic acid
COG ANBL1232 - Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients with Non-High- Risk Neuroblastoma
This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.
Emily Greengard
All
up to 18 Months old
Phase 3
NCT02176967
1410M54605
Inclusion Criteria:
• Patients must be:
• < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
• < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms neuroblastoma/ganglioneuroblastoma
• Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
• Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
• Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
• "Favorable" genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above
• "Unfavorable" genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)
• Only patients with MYCN non-amplified tumors are eligible for this study
• Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
• Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma
• No prior tumor resection or biopsy
• Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
• Group A1:
• > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR
• Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR
• < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter
• Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
• Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.]); horner syndrome is not considered neurologic compromise
• No prior tumor resection, tumor biopsy ONLY
• Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1 or APEC14B1
• Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms neuroblastoma/ganglioneuroblastoma
• No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with MYCN amplified tumors are not eligible
• Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
• Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study
Drug: Carboplatin, Other: Clinical Observation, Drug: Cyclophosphamide, Drug: Doxorubicin Hydrochloride, Drug: Etoposide, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study
Ganglioneuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Neuroblastoma
MT2015-32 : Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) for the Treatment of Hematological Diseases
This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion. It is a modification of the treatment plan which has been studied extensively over the last 10+ years which has shown consistent engraftment and low transplant related mortality (TRM).
Mark Juckett
All
up to 75 Years old
Phase 2
NCT02661035
1603M85362
Inclusion Criteria:
• Age, Performance Status, and Graft Criteria
• Age 0 to 70 years of age with Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
• Patients ≥ 70 and ≤ 75 years of age may be eligible if they have a HCT-CI Co-Morbidity score ≤ 2
• Must be ≥ 3 months after prior myeloablative transplant, if applicable
• 5/6 or 6/6 related donor match or a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor marrow and/or PBSC donor match per current institutional guidelines Related donors will be evaluated and collected per MT2012-14C; Unrelated donors will be identified and collected per usual procedures
• Eligible Diseases
• Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT-3 ITD +; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
• Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
• Acute Lymphocytic Leukemia (ALL): factor that define high risk CR1 include but are not limited to cytogenetics demonstrating t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
• Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
• Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
• Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
• Myelodysplasia (MDS) requiring transplant as defined as: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone marrow aspirate morphology.
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
• Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, NK cell malignancies are eligible after initial therapy in CR1+ or PR1+.
• Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
• Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
• Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
• Myeloproliferative Syndromes
• Organ Function Criteria Adequate organ function is defined as:
• Liver: AST and ALT < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
• Renal: Creatinine ≤ 2.0 mg/dl (adults) and estimated glomerular filtration rate (GFR) ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated glomerular filtration rate (GFR) > 40 mL/min.
• Albumin > 2.5 g/dL
• Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%.
• Pulmonary: DLCOcorr ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with or without exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
• If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
• Females of child bearing potential and sexually active males must agree to use adequate birth control during study treatment
• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
Exclusion Criteria:
• Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Untreated active infection
• Active CNS disease
• Active HIV infection or known HIV positive serology
• Congenital bone marrow failure syndrome
• Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of TBI
• CML in refractory blast crisis
• Intermediate or high grade NHL, mantle cell NHL, and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
• Multiple myeloma progressive on salvage chemotherapy
Drug: Allopurinol, Drug: Fludarabine, Drug: Cyclophosphamide, Drug: ATG, Radiation: TBI, Drug: Tacrolimus, Drug: MMF, Biological: Peripheral Blood Stem Cells, Biological: Related or Unrelated Bone Marrow Cells
Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myelodysplastic Syndromes, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Lymphoblastic Lymphoma, Burkitt's Lymphoma, Non-Hodgkin's Lymphoma, Multiple Myeloma, Myeloproliferative Syndromes, Hematological Diseases
AML, ALL, CML, MDS, CLL, SLL, NHL, Clinics and Surgery Center (CSC)
MT2015-17 :Transplantation of Umbilical Cord Blood from Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen
The primary objective is to estimate the probability of grade II-IV acute GVHD at Day 100 after unrelated donor umbilical cord blood transplantation using a non-myeloablative preparative regimen along with Sirolimus/MMF for GVHD prophylaxis in persons with hematologic malignancies.
Margaret MacMillan, MD
All
up to 75 Years old
Phase 2
NCT02722668
1603M84843
Inclusion Criteria:
• Age, Performance Status, and Graft Criteria
• <70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)
• Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
• UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
• Eligible Diseases All diseases listed below are advanced hematologic malignancies not curable by conventional chemotherapy. Responses to conventional treatment range from zero to 30% but are typically short lived.
• Acute Leukemias: Must be in remission by morphology (<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
• Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk. Favorable risk AML is defined as having one of the following:
• t(8,21) without cKIT mutation
• inv(16) or t(16;16) without cKIT mutation
• Normal karyotype with mutated NPM1 and wild type FLT-ITD
• Normal karyotype with double mutated CEBPA
• Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
• Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL. High risk ALL is defined as having one of the following:
• Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
• 30 years of age or older at diagnosis
• White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
• CNS leukemia involvement during the course of disease
• Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
• Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
• Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR
• Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts): Chronic phase patients must have failed at least two tyrosine kinase inhibitors, been intolerant to all available TKIs, or have T315I mutation.
• Myelodysplastic syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone marrow aspirate morphology. If ≥5% blasts, patient requires chemotherapy for cytoreduction to <5% blasts prior to transplantation.
• MRD positive leukemia (AML, ALL or accelerated/blast phase CML). Selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status.
• Leukemia or MDS in aplasia. These patients may be taken to transplant if after induction therapy they remain with aplastic bone marrow and no morphological or flow-cytometry evidence of disease ≥ 28 days post-therapy. These high risk patients will be analyzed separately.
• Burkitt's lymphoma in CR2 or subsequent CR
• Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed or ineligible for an autologous transplant.
• Natural killer cell malignancies
• Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease who are ineligible for an autologous transplant.
• Relapsed Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
• Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
• Relapsed Multiple Myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant.
• Plasma Cell Leukemia after initial therapy if achieved at least in partial remission; or relapsed and achieved subsequent remission (CR/PR)
• Acquired Bone marrow failure syndromes, except for Fanconi anemia
• Myeloproliferative Neoplasms/Myelofibrosis
• Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
• Additional Criteria for Bulky Disease (lymphomas)
• If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately)
• If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
• Organ Function Criteria Adequate organ function is defined as:
• Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%. For children that are not able to cooperate with MUGA and echocardiography, such should be clearly stated in the physician's note.
• Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
• Liver: Transaminases ≤ 5 x upper limit of normal (ULN) and total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis
• Renal: Creatinine ≤ 2.0 mg/dl (adults) and creatinine clearance ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated creatinine clearance ≥ 40 ml/min/1.73m^2. Adequate performance status is defined as Karnofsky score ≥ 70% (≥ 16 years of age) or Lansky score ≥ 50 (pediatrics)
• Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
Exclusion Criteria:
• Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
• Untreated active infection
• Active HIV infection or known HIV positive serology
• Less than 3 months since prior myeloablative transplant
• Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
• Active central nervous system malignancy
Drug: Fludarabine, Drug: Cyclophosphamide, Drug: MMF, Drug: Sirolimus, Radiation: TBI, Biological: Umbilical cord blood cell infusion, Biological: ATG
Acute Leukemia, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia/Lymphoma, Burkitt's Lymphoma, Natural Killer Cell Malignancies, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome, Large-cell Lymphoma, Hodgkin Lymphoma, Multiple Myeloma, Relapsed Chronic Lymphocytic Leukemia, Relapsed Small Lymphocytic Lymphoma, Marginal Zone B-cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-cell Lymphoma, Prolymphocytic Leukemia, Bone Marrow Failure Syndromes, Myeloproliferative Neoplasms/Myelofibrosis, Biphenotypic/Undifferentiated/Prolymphocytic Leukemias, MRD Positive Leukemia, Leukemia or MDS in Aplasia, Relapsed T-Cell Lymphoma, Relapsed Multiple Myeloma, Plasma Cell Leukemia
Clinics and Surgery Center (CSC), AML, ALL, CML, CLL, SLL
MT2016-15 :Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies
This is a two stage phase II trial of HLA-haploidentical related hematopoietic cells transplant (Haplo-HCT) using a reduced intensity conditioning (cyclophosphamide, fludarabine, melphalan, total body irradiation) with modifications based on factors including age and comorbidities. Bone marrow is the donor graft source. This study is designed to estimate disease-free survival (DFS) at 1 year posttransplant. Since the goal is to estimate the DFS at a long-term time-point (1 year post-transplant), the design is a generalization of the Simon design. Rather than suspension of the trial for evaluation after stage 1, this design uses an optimal interim analysis for futility without suspension of accrual.
Najla El Jurdi
All
up to 75 Years old
Phase 2
NCT02988466
1610M96901
Inclusion Criteria:
• Karnofsky performance status of ≥70% or Lansky play score ≥ 70%
• A related haploidentical bone marrow donor with up to 2 or 3 HLA locus-mismatches
• The donor and recipient must be HLA identical for at least one haplotype (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.
• Adequate liver and renal function
• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40%
• Diffusion capacity corrected (DLCOcorr) > 40% predicted, and absence of O2 requirements
• > 6 months after prior autologous transplant (if applicable)
• Agrees to use contraception during study treatment
• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
• Patients who are HIV+ must have undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation
Exclusion Criteria:
• < 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
• Pregnancy or breastfeeding
• Current active and uncontrolled serious infection
• Acute leukemia in morphologic relapse/persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods).
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy.
• stable non-bulky disease is acceptable.
• Active central nervous system malignancy Criteria For Donor Selection:
• Donors must be HLA-haploidentical relatives of the patient, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.
• Eligible donors (14-70 years old) include biological children, siblings or half siblings, or parents, able and willing to undergo bone marrow harvesting.
• For donors <18 years, the maximum recipient weight (actual body weight) should not exceed 1.25 times the donor weight (actual body weight)1 In addition, bone marrow product volume should be limited to 20 ml/kg donor weight for donors <18 years.
Biological: Haplo HCT <55 years old, Biological: Haplo HCT ≥55 years old, Drug: GVHD Prophylaxis, Biological: Haplo HCT ≥55 and < 65 years old, Biological: Haplo HCT ≥65 and ≤75 years old
Hematologic Malignancies
Acute Leukemias, Acute myeloid leukemia (AML), Acute lymphoblastic leukemia (ALL)/lymphoma, Biphenotypic/Undifferentiated/Prolymphocytic Leukemias, Myelodysplastic syndrome, Chronic myelogenous leukemia, Minimal Residual Disease (MRD) positive leukemia, Leukemia or Myelodysplastic Syndromes (MDS) in aplasia, Myeloproliferative neoplasms/myelofibrosis, Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma, Burkitt's lymphoma, Relapsed T-cell lymphoma, Natural Killer cell malignancies, Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, Lymphoplasmacytic lymphoma, Relapsed multiple myeloma, Bone marrow failure syndromes, Clinics and Surgery Center (CSC)
MT2016-11 :Autologous Stem Cell Transplant In Patients with Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphomas (NHL)
Veronika Bachanova, MD
All
up to 75 Years old
Phase 2
NCT03125642
1611M99805
Inclusion Criteria:
• Eligible Diseases
• Non-Hodgkin's Lymphoma (NHL)
• Patients with chemo-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic sub-classification.
• Patients in partial or complete remission following cell therapy will also be eligible.
• NHL patients with resistant or refractory lymphoma (no PR following up to three cycles of combination chemotherapy) will not be eligible for transplant in this trial.
• Lymphoblastic Lymphoma:
• All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
• Patients with any high-risk features will be eligible in first complete remission
• High risk features include: Stage IV, LDH >2 x upper limit of normal, ≥ 2 extranodal sites
• Mature B-cell Lymphoma
• Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2
• Diffuse Large B-Cell Lymphoma: in ≥ CR2 or ≥ PR1; a high intermediate or high IPI (≥ 2 for age-adjusted IPI or ≥3 for IPI) at diagnosis and double-hit or triple-hit lymphoma will be eligible in first CR; transformed lymphoma from FL (or other indolent lymphoma) or chronic lymphocytic leukemia will be eligible if chemosensitive and bone marrow is negative
• Mantle Cell Lymphoma: in first or greater CR or PR
• Burkitt's/Burkitt's like: all patients except localized lymphoma will be eligible any time after initial therapy (after achievement of first complete remission), or in partial remission if they fail to achieve CR; patients with localized (stage I or Ziegler stage A) will be eligible only if they fail to achieve CR1 or after relapse
• Mature T-Cell Lymphoma
• Chemosensitive T-cell lymphomas including Primary T-cell not otherwise specified angioimmunoblastic, and ALK-positive anaplastic large cell, will be eligible after initial therapy, whether or not CR is achieved.
• Mycosis fungoides/Sezary syndrome will be eligible in ≥CR2/PR2
• Hodgkin Lymphoma (HL)
• Patients with histologically proven HL will be eligible for transplantation after failing prior therapy.
• Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will not be eligible for transplant in this trial.
• For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
• For advanced (stage III/IV) Hodgkin disease, patients must have failed an Adriamycin containing regimen (ABVD) or an alternative non-cross resistant regimen (e.g. MOPP)
• Patients with any high-risk features will also be eligible, including those who:
• fail to achieve complete remission with initial combination chemotherapy
• have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass ≥ 5 cm or other residual mass ≥ 10 cm accompanied by other features of persisting disease (e.g., PET scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy
• Patients should receive chemotherapy to attempt to achieve CR or minimal disease state for all patients pre-transplantation. The use of up to three cycles of non-cross resistant combination chemotherapy is advised.
• Residual areas of limited disease should be considered for radiotherapy after and not prior to transplantation.
• HIV positive patients who are otherwise eligible for this study may be enrolled if they meet the following requirements:
• Are seen in the infectious disease (ID)/HIV clinic prior to enrollment on study for the purpose of determining eligibility and for local coordination of HIV care during the peri-transplant period.
• Are on maximally active anti-HIV regimen to control disease as determined appropriate by the ID/HIV physicians. For the majority of patients, this will be a highly active anti-retroviral therapy (HAART)-type therapy including a protease inhibitor.
• CD4+ ≥ 50/µL
• HIV RNA viral load ≤ 100,000 copies per mL on each of samples 4 weeks apart. The most recent level must be within 30 days of enrollment.
• Performance Status: Karnofsky Performance Status ≥ 80% for patients ≥ 16 years of age or Lansky Play Score ≥ 80 for patients < 16 years of age. Note: if poor performance status is due to lymphoma - KPS ≥ 60% or LPS ≥ 60 is acceptable
• Organ Function
• No evidence of serious organ dysfunction that is not attributable to tumor including:
• Hematologic:
• hemoglobin > 8 gm/dL
• WBC > 2.5 x 109/L with an ANC > 1.5 x 109/L off G-CSF or GM-CSF for 10 days or Neulasta for 21 days
• platelets > 100 x 109/L without transfusion
• bone marrow cellularity of > 20% with <5% involvement with tumor
• Renal: GFR > 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
• Hepatic: no history of severe prior or ongoing chronic liver disease. Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase <5x upper limit of normal
• Cardiac: free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia. The ejection fraction by gated cardiac blood flow scan (MUGA) or Echocardiogram must be >40%
• Pulmonary: no significant obstructive airways disease (FEV1 must be ≥ 50%) and must have acceptable diffusion capacity (corrected DLCO > 50% of predicted)
• Central Nervous System: Patients with a history of CNS involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for Cy/TBI arm. Patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment
• Other Inclusion Criteria
• At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment
• Patients who are carriers of Hepatitis B will be included in this study
• Voluntary written consent
Exclusion Criteria:
• Pregnant or breastfeeding: Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
• Eligible for any higher priority transplant protocols
• Chemotherapy resistant disease
• Unrelated active infection
Drug: Etoposide, Drug: BCNU, Drug: AraC, Drug: Melphalan, Procedure: Peripheral blood stem cell transplantation, Biological: G-CSF, Drug: Cyclophosphamide, Radiation: Total Body Irradiation
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Lymphoblastic Lymphoma, Mature B-cell Lymphomas, Follicular Lymphoma, Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, Burkitt's/Burkitt's like, Mature T-Cell Lymphoma, Clinics and Surgery Center (CSC)
MT2017-28 The Head Start 4 Protocol - Newly Diagnosed Children (less than 10 years old) with Medulloblastoma and Other Central Nervous System Embryonal Tumors: Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation with Either Single Cycle (Low Risk Patients) or Randomization (High Risk Patients) to Either Single-Cycle or to Three Tandem Cycles of Marrow-Ablative Chemotherapy with Autologous Hematopoietic Progenitor Cell Rescue Added Title: Neuroanatomical, Cognitive and Family Aspects to Recovery from a Brain Tumor
This is a prospective randomized clinical trial, to determine whether dose-intensive tandem Consolidation, in a randomized comparison with single cycle Consolidation, provides an event-free survival (EFS) and overall survival (OS). The study population (children < 120 months) will be high-risk patients (non-Wnt and non-Shh sub-groups) with medulloblastoma, and for all patients with central nervous system (CNS) embryonal tumors completing "Head Start 4" Induction. This study will further determine whether the additional labor intensity (duration of hospitalizations and short-term and long-term morbidities) associated with the tandem treatment is justified by the improvement in outcome. It is expected that the tandem (3 cycles) Consolidation regimen will produce a superior outcome compared to the single cycle Consolidation, given the substantially higher dose intensity of the tandem regimen, without significant addition of either short-term or long-term morbidities.
Christopher Moertel, MD
All
up to 10 Years old
Phase 4
NCT02875314
STUDY00000427
Inclusion Criteria:
• Patients 10 years of age at the time of definitive confirmatory eligible histologic or cytologic diagnosis of eligible CNS tumor (brain or spinal cord)
• Patients may not have received irradiation or chemotherapy (except corticosteroids)
• Have histologically proven diagnosis of medulloblastoma or CNS embryonal tumors of the brain or spinal cord
• Medulloblastoma
• Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (FFPE or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis
• Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis
• Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection
• CNS Embryonal Tumors:
• Pineoblastoma, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes (ETMR, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI1 intact) and CNS embryonal tumor, not otherwise specified.
• Must commence Induction chemotherapy within 28 days of the most recent definitive surgical procedure and within 21 days of the most recent neuro-imaging studies (MRI of brain, performed with and without gadolinium contrast, and MRI of total spine, performed with gadolinium contrast) and lumbar CSF cytological examination
• Patients must have adequate organ functions at the time of registration:
• Liver: bilirubin less than 1.5 mg/dL (except for patients with Gilbert's Syndrome of indirect hyperbilirubinemia) and transaminases [SGPT or ALT, and SGOT or AST] less than 2.5 (two and a half) times the upper limits of institutional normal.
• Renal: Creatinine clearance and/or glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m² within 21 days of protocol therapy.
• Bone Marrow Function:
• Peripheral absolute phagocyte count (APC) > 1000/ µL. APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = [percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils] x total white cell count.
• Platelet Count > 100,000/µL (transfusion independent)
• Hemoglobin > 8 gm/dL (may have received RBC transfusions).
Exclusion Criteria:
• Patients older than 10 years of age at time of diagnosis
• Following diagnoses are not eligible for study enrollment: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord; all choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas).
• Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.
Drug: Induction, Drug: Single Cycle Intensive Chemotherapy, Drug: Tandem 3 Cycle Intensive Chemotherapy
Medulloblastoma, Central Nervous System Embryonal Tumors
A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK PathwayMutant Acute Lymphoblastic Leukemia Protocol Number: AALL1521/INCB 18424-269
This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-ALL. Subjects with de novo B-ALL, aged 1 to 21 years at the time of diagnosis, will be evaluated for genetic eligibility during the Induction phase of a 4-drug regimen (modified augmented Berlin-Frankfurt-Münster (aBFM) or equivalent).
Peter Gordon
All
1 Year to 21 Years old
Phase 2
NCT02723994
1609M94601
Inclusion Criteria:
• Eligible for study when participant is 1 year to 21 years at the time of diagnosis
• Eligible Ages in Australia and Canada; 2 years to 21 years
• De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:
• Age ≥ 10 years
• White blood cell (WBC) ≥ 50 × 10^3/μL
• CNS3 leukemia at diagnosis
• Systemic steroid pretreatment without presteroid WBC documentation
• Diagnostic bone marrow or peripheral blood sample must have gene expression profiling and downstream genetic testing performed by submitting diagnostic specimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study. Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested by low density microarray testing at the COG ALL reference laboratory or TriCore laboratory at the University of New Mexico AND must contain 1 of the following genetic lesions: (determined at COG ALL reference laboratories, or equivalent CAP/CLIA-certified laboratories approved by the medical monitor:
• CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)
• CRLF2 rearrangement* without JAK mutation
• Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions, IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status*† as determined by a COG ALL Reference Laboratory
• Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or its successor study, or as per the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
• Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation
Exclusion Criteria:
• Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
• Trisomy 21 (Down syndrome)
• BCR-ABL1-rearranged (Ph+) ALL
• Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/min/1.73 m^2
• Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age
• Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)
• History or evidence of cirrhosis
• Platelet count < 75 × 10^3/μL
• Absolute neutrophil count (ANC) < 750/μL
• Positive screen for hepatitis B or C
• Known human immunodeficiency virus infection
Drug: Ruxolitinib, Drug: Asparaginase Erwinia Chrysanthemi, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisone, Drug: Thioguanine, Drug: Vincristine Sulfate
Leukemia
B-cell acute lymphoblastic leukemia (ALL), pediatric, multi-agent chemotherapy, JAK inhibitor
COG APEC14B1 The Project: Every Child Protocol: A Registry, Eligibility Screening, Biology and Outcome Study Additional Title: EVERYCHILD (APEC14B1) PCR - COG Foundation
This research trial studies the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.
Emily Greengard
All
up to 25 Years old
N/A
NCT02402244
1603M85344
Inclusion Criteria:
• Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
• Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
• Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
• All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of two "2" (carcinoma in situ) or three "3" (malignant)
• All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
• The following other benign/borderline conditions:
• Mesoblastic nephroma
• Teratomas (mature and immature types)
• Myeloproliferative diseases including transient myeloproliferative disease
• Langerhans cell histiocytosis
• Lymphoproliferative diseases
• Desmoid tumors
• Gonadal stromal cell tumors
• Subjects must be =< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network [NCTN]) therapeutic study, for which there is a higher upper age limit
• All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
• If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1
Other: Cytology Specimen Collection Procedure, Other: Medical Chart Review
Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Lymphoproliferative Disorder, Malignant Solid Neoplasm, Myeloproliferative Neoplasm, Stromal Neoplasm
COG APEC1621F - NCI-COG PEDIATRIC MATCH (MOLECULAR ANALYSIS FOR THERAPY CHOICE)- PHASE 2 SUBPROTOCOL OF ENSARTINIB IN PATIENTS WITH TUMORS HARBORING ALK OR ROS1 GENOMIC ALTERATIONS
The NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) study, referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using genomic sequencing technologies in refractory/recurrent tumors from children and adolescents with cancer. The NCI-COG Pediatric MATCH study (APEC1621) is considered one study under one IND consisting of a Master Version Control protocol, screening protocol component and multiple subprotocol components, with each component being contained in its own separate document. Each “component” consists of the protocol document and its associated informed consent document. The Master Version Control Protocol is the overarching administrative protocol that will keep an up-to-date record of the current version of the screening protocol component and each subprotocol component of Pediatric MATCH. Since each subprotocol component operates independently from the other subprotocol components contained in Pediatric MATCH, each has its own version date. Likewise, the screening protocol component has its own version date since changes in any of the subprotocols may not require changes in the screening protocol.
Emily Greengard
All
12 Months to 21 Years old
Phase 2
NCT03213652
STUDY00001752
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the presence of an actionable mutation
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on a standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment with other ALK inhibitors is permitted given that at least 5 half-lives or 21 days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for one week after the last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Drug: Ensartinib, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study
Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Recurrent WHO Grade 2 Glioma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor
Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
The NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) study, referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using genomic sequencing technologies in refractory/recurrent tumors from children and adolescents with cancer. The NCI-COG Pediatric MATCH study (APEC1621) is considered one study under one IND consisting of a Master Version Control protocol, screening protocol component and multiple subprotocol components, with each component being contained in its own separate document. Each “component” consists of the protocol document and its associated informed consent document. The Master Version Control Protocol is the overarching administrative protocol that will keep an up-to-date record of the current version of the screening protocol component and each subprotocol component of Pediatric MATCH. Since each subprotocol component operates independently from the other subprotocol components contained in Pediatric MATCH, each has its own version date. Likewise, the screening protocol component has its own version date since changes in any of the subprotocols may not require changes in the screening protocol.
Emily Greengard
All
12 Months to 21 Years old
Phase 2
NCT03213704
STUDY00001752
Inclusion Criteria:
• APEC1621SC: Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621A based on the presence of an actionable mutation as defined in APEC1621SC
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG)+ evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT); Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required time frame, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor leukocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial brain metastases (BM) radiation; Note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to other NTRK inhibitors including but not limited to LOXO-101 (larotrectinib), entrectinib (RXDX-101), DS6051, PLX7486
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL); male: 0.6 female: 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL); male: 0.8 female: 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL); male: 1 female: 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL); male: 1.2 female: 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL); male: 1.5 female: 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL); male: 1.7 female: 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Patients with seizure disorder may be enrolled if on anti-convulsants and well controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflect (DTR); any grade of DTR is eligible
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease (GVHD) post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients who have received prior therapy with a specific inhibitor of TRK (including but not limited to entrectinib [RXDX-101], DS-6051b, and PLX7486) are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Drug: Larotrectinib Sulfate
Advanced Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Wilms Tumor
COG APEC1621SC - NCI-COG PEDIATRIC MATCH (MOLECULAR ANALYSIS FOR THERAPY CHOICE) SCREENING PROTOCOL
The NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) study, referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using genomic sequencing technologies in refractory/recurrent tumors from children and adolescents with cancer. The NCI-COG Pediatric MATCH study (APEC1621) is considered one study under one IND consisting of a Master Version Control protocol, screening protocol component and multiple subprotocol components, with each component being contained in its own separate document. Each “component” consists of the protocol document and its associated informed consent document. The Master Version Control Protocol is the overarching administrative protocol that will keep an up-to-date record of the current version of the screening protocol component and each subprotocol component of Pediatric MATCH. Since each subprotocol component operates independently from the other subprotocol components contained in Pediatric MATCH, each has its own version date. Likewise, the screening protocol component has its own version date since changes in any of the subprotocols may not require changes in the screening protocol.
Emily Greengard
All
12 Months to 21 Years old
Phase 2
NCT03155620
STUDY00001752
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
• Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols
Procedure: Biopsy, Procedure: Biospecimen Collection, Drug: Ensartinib, Drug: Erdafitinib, Other: Laboratory Biomarker Analysis, Drug: Larotrectinib Sulfate, Procedure: Mutation Carrier Screening, Drug: Olaparib, Drug: Palbociclib, Other: Pharmacological Study, Drug: Samotolisib, Drug: Selpercatinib, Drug: Selumetinib Sulfate, Drug: Tazemetostat, Drug: Tipifarnib, Drug: Ulixertinib, Drug: Vemurafenib
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Langerhans Cell Histiocytosis, Malignant Glioma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor
Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
The NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) study, referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using genomic sequencing technologies in refractory/recurrent tumors from children and adolescents with cancer. The NCI-COG Pediatric MATCH study (APEC1621) is considered one study under one IND consisting of a Master Version Control protocol, screening protocol component and multiple subprotocol components, with each component being contained in its own separate document. Each “component” consists of the protocol document and its associated informed consent document. The Master Version Control Protocol is the overarching administrative protocol that will keep an up-to-date record of the current version of the screening protocol component and each subprotocol component of Pediatric MATCH. Since each subprotocol component operates independently from the other subprotocol components contained in Pediatric MATCH, each has its own version date. Likewise, the screening protocol component has its own version date since changes in any of the subprotocols may not require changes in the screening protocol.
Emily Greengard
All
12 Months to 21 Years old
Phase 2
NCT03213678
STUDY00001752
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621D based on the presence of an actionable mutation as defined in APEC1621SC; note that treatment assignment may be to primary cohort A for patients with TSC1 or TSC2 loss of function mutations or primary cohort B for patients with other PI3K/MTOR pathway mutations
• Patients accruing to dose level 1 must have a body surface area >= 0.52 m^2 at the time of study enrollment; patients accruing to dose level 2 must have a body surface area >= 0.37 m^2 at the time of study enrollment; patients accruing to dose level -1 must have a body surface area >= 0.75 m^2 at the time of study enrollment
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Bone lesions without an associated soft tissue mass >= 10 mm in greatest diameter; bone lesions with an associated soft tissue mass >= 10 mm in greatest diameter imaged by CT or MRI are considered measurable
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to LY3023414
• Patients must not have received prior exposure to an agent specifically directed at the PI3K/MTOR pathway (a PI3K inhibitor, an AKT inhibitor, an MTOR inhibitor, including rapalogs, or a combined PI3K/MTOR inhibitor)
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Patients must have a normal blood sugar level for age; if an initial random draw (i.e. non-fasting) blood glucose value is out of range, it is acceptable to repeat this test as a fasting draw
• Patients must have a serum triglyceride level =< 300 mg/dL and serum cholesterol level =< 300 mg/dL; if an initial random draw (i.e. non-fasting) is out of range, it is acceptable to repeat this test as a fasting draw
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Nervous system disorders (by Common Terminology Criteria for Adverse Events version
• 0 [CTCAE V 5.0]) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible
• Corrected QT (QTc) interval =< 480 milliseconds
• Patients must be able to swallow intact tablets
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while receiving study treatment and for 3 months after the last dose of LY3023414
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who have an uncontrolled infection are not eligible
• Patients who have insulin dependent diabetes are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients with subependymal giant cell astrocytomas (SEGAs) are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Drug: Samotolisib
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Malignant Glioma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Primary Central Nervous System Neoplasm, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor
A double-blind, randomized, vehicle controlled, crossover study to evaluate the safety and efficacy of topical naloxone hydrochloride lotion, 0.5%, for the relief of pruritus in patients with the mycosis fungoides (MF) form of cutaneous t-cell lymphoma (CTCL)
The primary objective is to evaluate the safety and efficacy of topically applied naloxone lotion, 0.5%, for the treatment of pruritus in patients with the mycosis fungoides (MF) or Sézary syndrome (SS) Forms of Cutaneous Tcell Lymphoma (CTCL).
Kim Bohjanen, MD
All
21 Years and over
Phase 3
NCT02811783
STUDY00002462
Inclusion Criteria:
All subjects must meet the following criteria for admission into the study:
• Signed informed consent has been obtained.
• Subject is at least 21 years of age.
• Diagnosis of mycosis fungoides (MF) or Sézary syndrome (SS) will be based on a combination of histological, clinical, and immunophenotypical criteria. The histological criteria will be based on skin biopsy from the most representative skin area. The diagnostic criteria used for each subject will be specified in the case report forms and the specific classification of MF or SS will be identified. The TNMB system will be used to classify the stage of disease (See Section 8.4 for details).
• Completion of the mSWAT assessment.
• A history of pruritus that meets following criteria: At Screening Day -7:
• present on a daily basis for greater than one month prior to Screening Day -7,
• NRS for Pruritus score ≥5 as rated by the subject at the Day -7 Visit. Note: If the score is <5 and subject is taking or has taken a medication which may be affecting pruritus (e.g. systemic antihistamine or topical steroid), and if Investigator and subject agree, subject may washout or continue washout of medication and return for Day -7 Visit procedures after washout. At Baseline Period 1 Day 0:
• NRS for Pruritus score of at least 5 recorded in the subject diary on at least 4 of the 7 days preceding Baseline Period 1 Day 0.
• Pruritic treatment area of 5-95% of the subject's total treatable body surface area.
• Subject can be expected to reliably follow treatment instructions and visit schedule.
• Non-pregnant, non-lactating females of childbearing potential who agree to use medically acceptable forms of birth control (abstinence, hormonal contraceptives, diaphragm with spermicide, condom with spermicide, or intrauterine device) throughout the study or females of non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal ≥ 1 year). A negative urine pregnancy test must be confirmed at Baseline screening for all female subjects who are not post-menopausal > 1 year or surgically sterile.
• The subject agrees not to begin any new concomitant medications during their participation in the study, with the exception of medications necessary to treat infection, and to continue any concomitant medication throughout the study.
• Subject has no visual or motor impairments that will make it difficult to complete the Daily Diary or apply the study medication.
• Subject is able to speak, read, and write English and agrees to participate and comply with the study procedures.
• Subject has a body mass index (BMI) between 18.5 and 30.5 kglm2 (see Appendix C, Body Mass Index Table) (subjects in PK subset only).
Exclusion Criteria:
Subjects meeting any of the following criteria will be excluded from study participation:
• Pregnant or lactating female.
• History of clinically significant heart failure.
• Myocardial infarction within the past six months.
• A history of ventricular arrhythmia requiring treatment.
• Any medical condition which would, in the Investigator's opinion, preclude the subject from successfully participating in the study.
• A known allergy to naloxone hydrochloride or any excipient in the formulation.
• Previous naloxone use for pruritus.
• Positive urine drug screen at Day 0 for opiates. Positive urine drug screen for anything other than opiates not explained, e.g., by concomitant medication, would also exclude the subject.
• Treatment with any of the following during the restricted time period prior to Day -7, and at any time during the study, is not allowed: Medication/Treatment Restriction: Systemic narcotic analgesics (e.g. morphine, codeine) 7 days, Topical antihistamines to any skin surface [e.g. Zonalon® (doxepin)] 7 days, Other investigational drugs (excluding any therapies for the treatment of MF or SS) 30 days
Drug: Naloxone Hydrochloride Lotion, 0.5%, Drug: Placebo Lotion
Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous, Sézary Syndrome
Pruritus, Mycosis Fungoides, CTCL, naloxone, opiate antagonist, Sézary Syndrome, Clinics and Surgery Center (CSC)
MT2015-29 : Myeloablative Allogeneic Hematopoietic Cell Transplantation Using a Related or Adult Unrelated Donor for the Treatment of Hematological Disorders
The primary research element is to determine whether a graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide, tacrolimus and MMF will reduce the likelihood of chronic GVHD in patients receiving a standard hematopoietic myeloablative stem cell transplant. The treatment related components of this protocol are established clinical practices and are considered non-investigational. The primary endpoint is cumulative incidence of chronic GVHD requiring systemic immunosuppressive treatment at 1 year post-transplant.
Shernan Holtan
All
up to 60 Years old
Phase 2
NCT03314974
STUDY00001087
-
• Age: ≤ 60 years of age
• Performance Status: Karnofsky ≥ 70%, Lansky play score ≥ 70
• Consent: Voluntary written consent (adult or legally authorized representative; or parental/guardian)
• Adequate Organ Function:
• Renal: Creatinine <2x upper limit of normal. Patients above this limit must have creatinine clearance ≥ 40 ml/min/1.73m2 as determined by an age-appropriate method, such as cystatin C GFR.
• Hepatic: Bilirubin, AST, alkaline phosphatase <4 times the upper limit of institutional normal
• Pulmonary: Diffusion capacity of oxygen, corrected for hemoglobin, > 50% of predicted. For pediatric patients not able to undergo PFTs or diffusion testing: O2 sat of >95% on room air
• Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 45%. For children not able to cooperate with MUGA or echocardiography, such should be clearly stated in the physician's documentation
• HIV Status: HIV infection with undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation Other
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program
• Eligible Diseases and Status: Patients are eligible unless their treatment is to be guided by a higher priority protocol.
• Acute Leukemias: Must be in remission by morphology (≤5% blasts). Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
• Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk.
• Favorable risk AML is defined as having one of the following:
• t(8,21) without cKIT mutation
• inv(16) or t(16;16) without cKIT mutation
• Normal karyotype with mutated NPM1 and wild type FLT-ITD
• Normal karyotype with double mutated CEBPA
• Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
• Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
• Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL.
• High risk ALL is defined as having one of the following:
• Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
• 30 years of age or older at diagnosis
• White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
• CNS leukemia involvement during the course of disease
• Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
• Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
• Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieve a complete remission.
• Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to one or more tyrosine kinase inhibitors.
• Plasma Cell Leukemia after initial therapy, in patients who have achieved at least a partial remission
• Myeloproliferative Neoplasms/Myelofibrosis, either primary as a result of polycythemia vera or essential thrombocythemia, with disease risk of intermediate or high-risk according to DIPSS criteria. Blasts must be <10% by bone marrow aspirate morphology.
• Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features. Blasts must be < 10% by a representative bone marrow aspirate morphology.
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.
• Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
• Diffuse large Cell NHL > CR/> PR: Patients in CR/PR with initial short remission (<6 months) are eligible, or those who have failed/or are not eligible for autologous transplant.
• Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
• Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
• Juvenile myelomonocytic leukemia
• Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR.
• MRD positive leukemia (AML, ALL or accelerated/blast phase CML). Selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status.
• Natural Killer Cell Malignancies
• Acquired Bone Marrow Failure Syndromes except for Fanconi Anemia or Dyskeratosis Congenita
• Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
• Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens)
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
• Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
• Active central nervous system malignancy
• if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
• Active HIV infection or known HIV positive serology
• active uncontrolled infection
• Pregnant or breastfeeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
Inclusion Criteria:
• Age: ≤ 60 years of age
• Performance Status: Karnofsky ≥ 70%, Lansky play score ≥ 70
• Consent: Voluntary written consent (adult or legally authorized representative; or parental/guardian)
• Adequate Organ Function:
• Renal: Creatinine <2x upper limit of normal. Patients above this limit must have creatinine clearance ≥ 40 ml/min/1.73m2 as determined by an age-appropriate method, such as cystatin C GFR.
• Hepatic: Bilirubin, AST, alkaline phosphatase <4 times the upper limit of institutional normal
• Pulmonary: Diffusion capacity of oxygen, corrected for hemoglobin, > 50% of predicted. For pediatric patients not able to undergo PFTs or diffusion testing: O2 sat of >95% on room air
• Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 45%. For children not able to cooperate with MUGA or echocardiography, such should be clearly stated in the physician's documentation
• HIV Status: HIV infection with undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation Other
Inclusion Criteria:
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program
• Eligible Diseases and Status: Patients are eligible unless their treatment is to be guided by a higher priority protocol.
• Acute Leukemias: Must be in remission by morphology (≤5% blasts). Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
• Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk.
• Favorable risk AML is defined as having one of the following:
• t(8,21) without cKIT mutation
• inv(16) or t(16;16) without cKIT mutation
• Normal karyotype with mutated NPM1 and wild type FLT-ITD
• Normal karyotype with double mutated CEBPA
• Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
• Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
• Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL.
• High risk ALL is defined as having one of the following:
• Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
• 30 years of age or older at diagnosis
• White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
• CNS leukemia involvement during the course of disease
• Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
• Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
• Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieve a complete remission.
• Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to one or more tyrosine kinase inhibitors.
• Plasma Cell Leukemia after initial therapy, in patients who have achieved at least a partial remission
• Myeloproliferative Neoplasms/Myelofibrosis, either primary as a result of polycythemia vera or essential thrombocythemia, with disease risk of intermediate or high-risk according to DIPSS criteria. Blasts must be <10% by bone marrow aspirate morphology.
• Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features. Blasts must be < 10% by a representative bone marrow aspirate morphology.
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.
• Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
• Diffuse large Cell NHL > CR/> PR: Patients in CR/PR with initial short remission (<6 months) are eligible, or those who have failed/or are not eligible for autologous transplant.
• Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
• Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
• Juvenile myelomonocytic leukemia
• Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR.
• MRD positive leukemia (AML, ALL or accelerated/blast phase CML). Selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status.
• Natural Killer Cell Malignancies
• Acquired Bone Marrow Failure Syndromes except for Fanconi Anemia or Dyskeratosis Congenita
• Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
Exclusion Criteria:
• Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens)
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
• Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
• Active central nervous system malignancy
• if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
• Active HIV infection or known HIV positive serology
• active uncontrolled infection
• Pregnant or breastfeeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
Biological: HSCT with TBI Regimen, Biological: HSCT with Non-TBI Regimen
Acute Leukemia, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Lymphoma, Chronic Myelogenous Leukemia, Plasma Cell Leukemia, Myeloproliferative Neoplasms, Myelofibrosis, Myelodysplasia, Refractory Anemia, High Risk Anemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, Diffuse Large Cell Non Hodgkins Lymphoma, Lymphoblastic Lymphoma, Burkitt Lymphoma, High Grade Non-Hodgkin's Lymphoma, Adult, Multiple Myeloma, Juvenile Myelomonocytic Leukemia, Biphenotypic/Undifferentiated/Prolymphocytic Leukemias, MRD Positive Leukemia, Natural Killer Cell Malignancies, Acquired Bone Marrow Failure Syndromes
AML, ALL, MDS, NHL, CLL, CML, SLL, Clinics and Surgery Center (CSC)
Neoadjuvant therapy for patients with high risk stage III melanoma: a pilot clinical trial (NeoACTIVATE)
To estimate the percentage of patients with stage III BRAFm melanoma that achieves a pathologic complete response after 12 weeks of neoadjuvant vemurafenib/cobimetinib/atezolizumab. To estimate the percentage of patients with stage III BRAFwt melanoma that achieves a pathologic complete response after 12 weeks of neoadjuvant cobimetinib/atezolizumab. Adjuvant phase primary objectives: To assess recurrence-free survival (RFS) in patients with stage III BRAFm melanoma after neoadjuvant vemurafenib/cobimetinib/atezolizumab, surgery, and adjuvant atezolizumab. To assess RFS in patients with stage III BRAFwt melanoma after neoadjuvant cobimetinib/atezolizumab, surgery, and adjuvant atezolizumab.
Evidio Domingo Musibay
All
18 Years and over
Phase 2
NCT03554083
STUDY00004666
Inclusion Criteria:
• PRE-REGISTRATION: High-risk stage III melanoma, defined as (any of the following):
• Recurrent nodal metastasis, or
• Clinically detectable nodal metastasis, or
• Metastatic involvement of more than one nodal basin
• NOTE: For the purpose of pre-registration, high-risk stage III melanoma is defined based on clinical and imaging assessment (positron emission tomography/computed tomography [PET/CT], CT, or magnetic resonance imaging [MRI]). Histologic confirmation of nodal metastatic disease is not needed at the time of pre-registration, provided there is histologic confirmation of primary melanoma or a prior lymph node metastasis.
• PRE-REGISTRATION: Willing to submit archival tissue from a lymph node biopsy or undergo a needle biopsy (with clip placement) for BRAF testing and for research purposes.
• PRE-REGISTRATION: Willing to forego anticancer treatments or investigational agents during pre-registration period.
• PRE-REGISTRATION: The following laboratory values obtained =< 28 days prior to pre-registration:
• Only for patients receiving therapeutic anticoagulation: stable anticoagulant regimen and stable international normalized ratio (INR).
• REGISTRATION: Histologic confirmation of stage III melanoma, as defined by the American Joint Committee on Cancer, 8th revised edition.
• REGISTRATION: Documentation of BRAFV600 mutation status in melanoma tumor tissue (archival or newly obtained) through use of a Clinical Laboratory Improvement Amendments (CLIA)-approved clinical mutation test.
• REGISTRATION: Surgically resectable disease, as determined by a melanoma surgical oncologist.
• REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• REGISTRATION: Life expectancy >= 26 weeks.
• REGISTRATION: Absolute neutrophil count (ANC) >= 1500/mm^3 obtained =< 14 days prior to registration.
• REGISTRATION: Platelet count >= 100,000/mm^3 obtained =< 14 days prior to registration.
• REGISTRATION: Hemoglobin >= 9.0 g/dL obtained =< 14 days prior to registration.
• REGISTRATION: Direct bilirubin =< institutional upper limit of normal (ULN) obtained =< 14 days prior to registration.
• REGISTRATION: Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2 x ULN obtained =< 14 days prior to registration.
• REGISTRATION: Alkaline phosphatase < 2.5 x ULN obtained =< 14 days prior to registration.
• REGISTRATION: Creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 45 mL/min on the basis of measured CrCl from a 24-hour urine collection or Cockcroft-Gault glomerular filtration rate estimation obtained =< 14 days prior to registration.
• REGISTRATION: Arms A and B only: Left ventricular ejection fraction (LVEF) >= 50% or institutional lower limit of normal (LLN) =< 6 months prior to registration.
• REGISTRATION: Arms A and B only: Average corrected QT interval (QTc) =< 450 ms on triplicate 12 lead electrocardiography (ECG) =< 28 days prior to registration.
• NOTE: QTc intervals will be corrected using Fridericia's formula.
• REGISTRATION: Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only.
• REGISTRATION: For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment.
• REGISTRATION: For persons able to father a child: agreement to remain abstinent (refrain from heterosexual intercourse with a person of childbearing potential) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 6 months after the last dose of study treatment.
• REGISTRATION: Provide written informed consent.
• REGISTRATION: Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
• REGISTRATION: Willing to provide tissue, blood, and stool samples for correlative research purposes.
• REGISTRATION: Arm C Only: Negative serology for acute Epstein-Barr virus (EBV) infection (negative EBV viral capsid antigen [VCA] immunoglobulin M [IgM]).
Exclusion Criteria:
• PRE-REGISTRATION: Prior systemic anti-cancer therapy for melanoma (e.g., chemotherapy, hormonal therapy, targeted therapy, immunotherapy including anti-PD-1, anti-PDL1 agents, or other biologic therapies), with the following exceptions: adjuvant treatment with interferon, IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF) or vaccine therapies are allowed, if discontinued >= 28 days prior to pre-registration.
• PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• PRE-REGISTRATION: For patients with concurrent diagnosis of primary melanoma with nodal involvement, major surgical procedure other than lymph node biopsy or wide local excision of primary melanoma =< 4 weeks prior to pre-registration, or anticipation of need for a major surgical procedure for reasons other than melanoma during the course of the study.
• PRE-REGISTRATION: For patients with nodal recurrence, surgical procedure or anti-cancer therapy for this recurrence (other than lymph node biopsy) or anticipation of need for a major surgical procedure for reasons other than melanoma during the course of the study.
• PRE-REGISTRATION: Prior radiotherapy for melanoma.
• PRE-REGISTRATION: History of non-nodal melanoma metastasis or central nervous system (CNS) lesion(s) proven or clinically suspected to be metastasis.
• PRE-REGISTRATION: Active malignancy (other than melanoma) or malignancy =< 3 years prior to pre-registration.
• NOTE: Exceptions: Asymptomatic papillary thyroid cancer (not requiring treatment), resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ of the breast, in situ prostate cancer, non-muscle-invasive bladder cancer, Stage I uterine cancer, or other curatively treated malignancies from which the patient has been disease-free for at least 3 years prior to pre registration.
• PRE-REGISTRATION: Prior allogeneic stem cell or solid organ transplantation.
• PRE-REGISTRATION: History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• PRE-REGISTRATION: History of autoimmune disease requiring systemic immunosuppressive or immune-modulatory therapy =< 5 years prior to pre-registration.
• NOTE: Exceptions are allowed for hypothyroidism on thyroid replacement therapy; or Type 1 diabetes on insulin regimen.
• PRE-REGISTRATION: Active psoriasis requiring therapy (systemic or topical).
• PRE-REGISTRATION: Known clinically significant liver disease, including alcoholism, cirrhosis, fatty liver, and other inherited liver disease as well as active viral disease.
• PRE-REGISTRATION: Arms A and B only: History of or evidence of retinal pathology on ophthalmologic examination including but not limited to:
• Neurosensory retinal detachment
• Central serous chorioretinopathy
• Retinal vein occlusion (RVO)
• Neovascular macular degeneration
• PRE-REGISTRATION: Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• PRE-REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection (including but not limited to tuberculosis)
• Clinically significant cardiac dysfunction including:
• Symptomatic congestive heart failure defined as New York Heart Association class II or higher
• Unstable angina pectoris or new-onset angina =< 3 months prior to pre-registration
• Unstable cardiac arrhythmia
• Myocardial infarction =< 3 months prior to pre-registration
• Congenital long QT syndrome
• Clinically significant stroke, reversible ischemic neurological defect, or transient ischemic attack =< 6 months prior to pre-registration
• Any grade 3 hemorrhage or bleeding event =< 4 weeks prior to pre-registration
• Uncontrolled diabetes or symptomatic hyperglycemia
• Psychiatric illness/social situations that, in the judgement of the investigator, would: a) limit compliance with study requirements, or b) make the patient inappropriate for entry into this study, or c) interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• PRE-REGISTRATION: Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells (example [ex]: recombinant follicle-stimulating hormone [FSH]).
• PRE-REGISTRATION: Known hypersensitivity to any components of the atezolizumab (all arms), tiragolumab (Arm C only), cobimetinib (Arms A and B only), or vemurafenib (Arms A and B only) formulations.
• PRE-REGISTRATION: History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• REGISTRATION: Received anticancer treatments or investigational agents during pre-registration period.
• REGISTRATION: Clinically suspected non-nodal metastatic melanoma.
• REGISTRATION: Arm A only: For BRAF-mutant patients only: anticipated use of any concomitant medication =< 7 days prior to registration that is known to cause QT prolongation (which may lead to torsade de pointes).
• REGISTRATION: Arms A and B only: History of malabsorption or other clinically significant metabolic dysfunction that may interfere with absorption of oral study treatment or inability or unwillingness to swallow oral medication.
• REGISTRATION: Signs or symptoms of infection or has received antibiotics =< 14 days prior to registration.
• NOTE: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• REGISTRATION: Any of the following because this study involves investigational agents whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• REGISTRATION: Treatment with a live, attenuated vaccine =< 4 weeks prior to registration, or anticipation of need for such a vaccine during the course of the study.
• REGISTRATION: Treatment with systemic immunosuppressive medication (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF)-alpha agents) =< 2 weeks prior to registration, or anticipation of need for systemic immunosuppressive medication during the course of the study.
• NOTE: Patients who have received acute, low-dose systemic steroids (=< 10 mg/day oral prednisone or equivalent) prior to registration or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
• NOTE: The use of inhaled corticosteroids for chronic obstructive pulmonary disease or asthma, mineralocorticoids (e.g., fludrocortisone), or low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• REGISTRATION: Requirement for concomitant therapy or food that is prohibited during the study.
• REGISTRATION: Arms A and B only: Inability to abstain from alcohol during neoadjuvant phase.
• REGISTRATION: Arm C only: Known Epstein-Barr virus (EBV) infection.
• NOTE: Patients with symptoms such as splenomegaly, fever, sore throat, non-malignant cervical lymphadenopathy, and/or tonsillar exudate, should undergo an EBV polymerase chain reaction (PCR) test to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
Drug: Atezolizumab, Drug: Cobimetinib, Biological: Tiragolumab, Drug: Vemurafenib
Clinical Stage III Cutaneous Melanoma AJCC v8, Pathologic Stage III Cutaneous Melanoma AJCC v8, Pathologic Stage IIIA Cutaneous Melanoma AJCC v8, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIC Cutaneous Melanoma AJCC v8, Pathologic Stage IIID Cutaneous Melanoma AJCC v8
Clinics and Surgery Center (CSC)
Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
This phase II trial studies how well trametinib works in treating patients (≥ 2 years and < 22 years of age) with juvenile myelomonocytic leukemia that has come back or does not respond to treatment. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Emily Greengard
All
1 Month to 21 Years old
Phase 2
NCT03190915
STUDY00003883
Inclusion Criteria:
• Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria
• JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis
• Splenomegaly
• > 1000 (1 x 10^9/uL) circulating monocytes
• < 20% blasts in the bone marrow or peripheral blood
• Absence of the t(9;22) or BCR/ABL fusion gene
• JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
• Somatic mutation in RAS or PTPN11
• Clinical diagnosis of NF1 or NF1 gene mutation
• Homozygous mutation in CBL
• Monosomy 7
• JMML category 3 (at least two of the following if no category 2 criteria are met):
• Circulating myeloid precursors
• White blood cell count, > 10 000 (10 x 10^9/ uL)
• Increased hemoglobin F for age
• Clonal cytogenetic abnormality
• GM-CSF hypersensitivity
• Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes of any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
• Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
• Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy
• Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
• Monoclonal antibodies:
• At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
• Radiotherapy:
• >= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port)
• >= 6 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received
• >= 4 weeks must have elapsed if other substantial bone marrow irradiation was given
• Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 3 months must have elapsed since transplant; >= 4 weeks must have elapsed since any donor lymphocyte infusion
• Patients must not be known to be refractory to red blood cell or platelet transfusions
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: Maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male) 0.4 (female)
• 6 months to < 1 year: 0.5 (male) 0.5 (female)
• 1 to < 2 years: 0.6 (male) 0.6 (female)
• 2 to < 6 years: 0.8 (male) 0.8 (female)
• 6 to < 10 years: 1 (male) 1 (female)
• 10 to < 13 years: 1.2 (male) 1.2 (female)
• 13 to < 16 years: 1.5 (male) 1.4 (female)
• >= 16 years: 1.7 (male) 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 135 U/L) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by multi-gated acquisition (MUGA)
• Corrected QT (by Bazett's formula [QTcB]) interval < 450 msecs
• Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed
Exclusion Criteria:
• Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus
• Concomitant Medications
• Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
• Anti-graft versus host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Cardiac medications: any medications for treatment of left ventricular systolic dysfunction
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible
• Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
• Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension
• Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =< the 95th percentile for age, height, and gender
• Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible
• Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll
Drug: Trametinib
Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1
MT-2018-20: COG AALL1631 - International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones
This randomized phase III trial studies how well imatinib mesylate and combination chemotherapy work in treating patients (> 1 year and < 21 years) with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving imatinib mesylate and combination chemotherapy may work better in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
Peter Gordon
All
1 Year to 21 Years old
Phase 3
NCT03007147
STUDY00003635
Inclusion Criteria:
• Diagnostic samples will be collected and analyzed according to the procedures of the National front-line protocol
• Patients should be enrolled on National ALL protocol prior to enrollment on EsPhALL2017/COGAALL1631. Regardless of initial front-line protocol baseline diagnostic samples must be available to develop an MRD probe
• BCR-ABL1 fusion (Ph+): newly diagnosed ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO] definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-PCR
• ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions identified according to National/Center procedures of each participating country. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA, LYN. Methods of detection include fluorescence in-situ hybridization (FISH, e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole transcriptome or panel-based ribonucleic acid (RNA)-sequencing
• Regardless of initial front-line protocol, laboratory reports detailing evidence of BCR-ABL1 or ABL-class fusion must be available for the National Trial Unit
• Ph+ ALL patients must have previously started induction therapy, which includes vincristine, a corticosteroid, usually PEG-L-asparaginase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
• Ph+ ALL patients have not received more than 14 days of multiagent induction therapy beginning with the first dose of vincristine
• Ph+ ALL patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib
• ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy
• ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vincristine dose
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
• Direct bilirubin =< 2.0 mg/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT interval, QTc < 480 msec
• Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis, before study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Exclusion Criteria:
• Known history of chronic myelogenous leukemia (CML)
• ALL developing after a previous cancer treated with cytotoxic chemotherapy
• Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
• Down syndrome
• Pregnancy and breast feeding
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of treatment according to protocol
• Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block
• Prior treatment with dasatinib, or any TKI inhibitor other than imatinib
• All patients and/or their parents or legal guardians must sign a written informed consent
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Dexrazoxane Hydrochloride, Drug: Doxorubicin, Drug: Etoposide, Biological: Filgrastim, Drug: Ifosfamide, Drug: Imatinib Mesylate, Other: Laboratory Biomarker Analysis, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Pegaspargase, Drug: Prednisolone, Other: Questionnaire Administration, Drug: Therapeutic Hydrocortisone, Drug: Thioguanine, Drug: Vincristine Sulfate
Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia
COG AHEP1531 - Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)
This partially randomized phase II/III trial studies how well cisplatin and combination chemotherapy works in treating children and young adults (≤ 30 years of age) with hepatoblastoma or liver cancer after surgery. Drugs used in chemotherapy, such as cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy after surgery may kill more tumor cells.
Emily Greengard
All
up to 30 Years old
Phase 2/Phase 3
NCT03533582
STUDY00003718
Inclusion Criteria:
• Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must be newly diagnosed with histologically-proven primary pediatric hepatic malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified, should be classified and treated per hepatoblastoma treatment arms; note that rapid central pathology review is required in some cases; please note: all patients with histology as assessed by the institutional pathologist consistent with pure small cell undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by immunohistochemistry (IHC) according to the practices at the institution
• Patients with histology consistent with pure SCU must have positive INI1/SMARCB1 staining
• For all Group A patients, WDF status as determined by rapid review will be used to further stratify patients to Group A1 or A2
• For Groups B, C and D, rapid review is required if patients are either >= 8 years of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
• For all Groups E and F patients, rapid central pathology review is required
• In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy
• Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:
• Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
• Uncorrectable coagulopathy
• For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:
• The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment
• Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment
• Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
• Patients may have had surgical resection of the hepatic malignancy prior to enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• Age: maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 06 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 5 x upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 10 x upper limit of normal (ULN) for age
• Shortening fraction of >= 28% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment) or
• Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment)
• Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males and =< 470 milliseconds for females (assessed within 8 weeks prior to study enrollment)
• Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy [Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anticancer agents
• Patients with uncontrolled infection
• Patients who previously received a solid organ transplant, other than those who previously received an orthotopic liver transplantation (OLT) as primary treatment of their hepatocellular carcinoma
• Patients with hypersensitivity to any drugs on their expected treatment arm
• Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
• Group D:
• Patients with chronic inflammatory bowel disease and/or bowel obstruction
• Patients with concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
• Group F:
• Patients with peripheral sensitive neuropathy with functional impairment
• Patients with a personal or family history of congenital long QT syndrome
• These criteria apply ONLY to patients who may receive chemotherapy (all groups other than Group E1):
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• Note for Group F: patients of childbearing potential should use effective birth control during treatment with sorafenib and for at least 2 weeks after stopping treatment
Drug: Carboplatin, Drug: Cisplatin, Drug: Doxorubicin, Drug: Etoposide, Drug: Fluorouracil, Drug: Gemcitabine, Drug: Irinotecan, Other: Laboratory Biomarker Analysis, Drug: Oxaliplatin, Other: Patient Observation, Drug: Sorafenib, Drug: Vincristine Sulfate
Childhood Hepatocellular Carcinoma, Childhood Malignant Liver Neoplasm, Fibrolamellar Carcinoma, Hepatoblastoma, Hepatocellular Malignant Neoplasm, Not Otherwise Specified
COG ACNS1422 - A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients
Patients greater than or equal to 3 years of age and < 22 years of age with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma using reduced craniospinal radiotherapy.
Christopher Moertel, MD
All
3 Years to 21 Years old
Phase 2
NCT02724579
STUDY00002501
Inclusion Criteria:
• Patients must be newly diagnosed and have:
• Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1:
• Classical histologic type (non LC/A) WNT medulloblastoma
• Positive nuclear beta-catenin by immunohistochemistry (IHC)
• Positive for CTNNB1 mutation
• Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)
• Patient must have negative lumbar cerebrospinal fluid (CSF) cytology
• Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF; ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status; patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated; patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
• Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1; patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with gadolinium must be performed
• Patients must be enrolled, and protocol therapy must be projected to begin, no later than 36 days after definitive diagnostic surgery (day 0)
• Peripheral absolute neutrophil count (ANC) >= 1000/uL
• Platelet count >= 100,000/uL (transfusion independent)
• Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and females)
• 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)
• 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)
• 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)
• >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
• The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
• Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN); for the purpose of this study, the ULN for SGPT is 45 U/L
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Patients must not be in status epilepticus, a coma or on assisted ventilation at the time of study enrollment
• Patients must have receptive and expressive language skills in English, French, or Spanish to complete the QoL and neurocognitive assessments; if a patient meets these criteria but the parent/guardian speaks a language other than English, French, or Spanish, the patient may still be enrolled and tested, and the parent-report measures should be omitted
• All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
• Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
• Pregnancy and Breast Feeding
• Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies
• Lactating females are not eligible unless they have agreed not to breastfeed their infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
• Patients with a history of moderate to profound intellectual disability (i.e., intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE: Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a specific learning disability (e.g., dyslexia) are eligible for this study
Drug: Cisplatin, Drug: Cyclophosphamide, Other: Laboratory Biomarker Analysis, Drug: Lomustine, Radiation: Radiation Therapy, Drug: Vincristine, Drug: Vincristine Sulfate
Medulloblastoma
MT2018-19: COG ANBL1531 - A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or ALK Inhibitor Therapy Added to Intensive Therapy for Children with Newly Diagnosed High-Risk Neuroblastoma (NBL) (IND# 134379)
This partially randomized phase III trial studies iobenguane I-131 or ALK Inhibitor Therapy and standard therapy in treating younger patients (365 days to 30 years of age) with newly-diagnosed high-risk neuroblastoma or ganglioneuroblastoma.
Emily Greengard
All
365 Days to 30 Years old
Phase 3
NCT03126916
STUDY00003568
Inclusion Criteria:
• Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
• Patient must be >= 365 days and =< 30 years of age at diagnosis
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
• Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• Age > 547 days regardless of biologic features
• Patients with INRG stage MS disease with MYCN amplification
• Patients with INRG stage L2 disease with MYCN amplification
• Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
• Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
• Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
• 1 to < 2 years: male = 0.6; female = 0.6
• 2 to < 6 years: male = 0.8; female = 0.8
• 6 to < 10 years: male = 1; female = 1
• 10 to < 13 years: male = 1.2; female = 1.2
• 13 to < 16 years: male = 1.5; female = 1.4
• >= 16 years: male = 1.7; female = 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
• No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
• Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
• Patients with bone marrow failure syndromes
• Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: Busulfan, Drug: Carboplatin, Drug: Cisplatin, Drug: Cyclophosphamide, Drug: Dexrazoxane Hydrochloride, Biological: Dinutuximab, Drug: Doxorubicin Hydrochloride, Drug: Etoposide Phosphate, Radiation: External Beam Radiation Therapy, Radiation: Iobenguane I-131, Drug: Isotretinoin, Drug: Lorlatinib, Drug: Melphalan Hydrochloride, Biological: Sargramostim, Procedure: Therapeutic Conventional Surgery, Drug: Thiotepa, Drug: Topotecan Hydrochloride, Drug: Vincristine Sulfate
Ganglioneuroblastoma, Neuroblastoma
A Phase II Study of Pembrolizumab Monotherapy in Recurrent Ovarian Cancer of the Immunoreactive Subtype determined by NanoString Gene Expression Profiling
To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on ORR as assessed by the investigator per irRECIST in patients with ROC whose tumors show an immunoreactive gene expression signature
Boris Winterhoff
Female
18 Years and over
Phase 2
NCT03732950
STUDY00006054
Inclusion Criteria:
• Be willing and able to provide written informed consent/assent for the trial
• Have received 1-5 prior lines for treating ROC (i.e. 2-6 total prior lines counting the front line) and must have a platinum-free interval (PFI) or a treatment-free interval (TFI) >= 3 months based on the last regimen received
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
• 1
• Note: Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Have histologically diagnosed recurrent epithelial ovarian, fallopian or primary peritoneal ovarian cancer
• Have provided a tumor tissue sample either collected from a newly obtained tumor tissue biopsy or an archival tissue specimen. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived biopsy specimen. Formalin-fixed paraffin embedded (FFPE) block specimens are preferred to 20 unstained slides. Additional samples may be requested if tumor tissue provided is not adequate for quality and/or quantity as assessed by the central laboratory
• Performed within 10 days of treatment initiation: absolute neutrophil count (ANC) >= 1,500/mcL
• Performed within 10 days of treatment initiation: platelets >= 100,000/mcL
• Performed within 10 days of treatment initiation: hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Performed within 10 days of treatment initiation: serum creatinine OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) =< 1.5 x upper limit of normal (ULN) OR >= 45 mL/min for subject with creatinine levels > 1.5 x institutional ULN
• Creatinine clearance should be calculated per institutional standard
• Performed within 10 days of treatment initiation: serum total bilirubin =<1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
• Performed within 10 days of treatment initiation: aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase [SGOT]) and aspartate aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Have received front line platinum-based chemotherapy (preoperative chemotherapy is allowed)
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Exclusion Criteria:
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received a live vaccine within 30 days of planned start of study therapy
• Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Biological: Pembrolizumab
Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
Clinics and Surgery Center (CSC)
MT2017-17: T cell receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients with Fanconi Anemia (FA)
The primary objective is to determine the incidence of grade II-IV acute graft versus host disease (GVHD) by Day 100 using an alpha/beta T cell depleted peripheral blood stem cells (PBSC) and without routine GVHD prophylaxis.
Margaret MacMillan, MD
All
up to 65 Years old
Phase 2
NCT03579875
STUDY00003182
Patient Selection:
• Diagnosis of Fanconi anemia
• Less than 65 years of age
• Karnofsky performance status of ≥ 70% or, for children < 16 years of age, Lansky Play Score ≥ 50
• Presence of at least one of the following risk factors:
• Severe aplastic anemia (SAA) defined as: Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:
• platelet count <20 x 109/L
• absolute neutrophil count of <5 x 108/L
• hemoglobin <8 g/dL
• Myelodysplastic syndrome (MDS) or acute leukemia
• High risk genotype
• Adequate organ function defined as:
• Bilirubin, AST or ALT, ALP <5 x normal, Cardiac: left ventricle ejection fraction (LEFV) ≥45% by ECHO
• Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
• Identification of a suitable donor for peripheral blood cells per match criteria found in Section 5.
• Females of childbearing potential and males with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months after the transplant
• Able to provide written voluntary consent prior to the performance of any research related tests or procedures with parental/guardian consent for minor (and assent as appropriate)
• Pregnant or breastfeeding as the treatment used in this study are Pregnancy Category D. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
• Active, uncontrolled infection within 1 week prior to starting study therapy
• Malignant solid tumor cancer within previous 2 years Donor Selection (Inclusion Criteria): meets one of the following match criteria:
• an HLA-A, B, DRB1 matched sibling donor (matched sibling)
• an HLA-A, B, DRB1 matched related donor (other than sibling)
• a related donor mismatched at 1 HLA-A, B, C and DRB1 antigen
• 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor per current institutional guidelines Patients and donors are typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. If a donor has been selected on the basis of HLA-A, B, C and DRB1 typing as above, preference will be made for donors matched at the HLA-C locus.
• Body weight of at least 40 kilograms and at least 12 years of age
• Willing and able to undergo mobilized peripheral blood apheresis
• In general good health as determined by the medical provider
• Adequate organ function defined as:
• Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• Hepatic: ALT < 2 x upper limit of normal
• Renal: serum creatinine < 1.8 mg/dl
• Performance of a donor infectious disease screen panel including CMV Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV 1/2 Antibody, HTLVA 1/2 Antibody, Treponema, and Trypanosoma Cruzi (T. Cruzi) plus HBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of and risks factors for infection with Zika virus, or per current standard institutional donor screen - must be negative for HIV and active hepatitis B
• Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
• Voluntary written consent (parent/guardian and minor assent, if < 18 years) prior to the performance of any research related procedure
Inclusion Criteria:
• Diagnosis of Fanconi anemia
• Less than 65 years of age
• Karnofsky performance status of ≥ 70% or, for children < 16 years of age, Lansky Play Score ≥ 50
• Presence of at least one of the following risk factors:
• Severe aplastic anemia (SAA) defined as: Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:
• platelet count <20 x 109/L
• absolute neutrophil count of <5 x 108/L
• hemoglobin <8 g/dL
• Myelodysplastic syndrome (MDS) or acute leukemia
• High risk genotype
• Adequate organ function defined as:
• Bilirubin, AST or ALT, ALP <5 x normal, Cardiac: left ventricle ejection fraction (LEFV) ≥45% by ECHO
• Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
• Identification of a suitable donor for peripheral blood cells per match criteria found in Section 5.
• Females of childbearing potential and males with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months after the transplant
• Able to provide written voluntary consent prior to the performance of any research related tests or procedures with parental/guardian consent for minor (and assent as appropriate)
Exclusion Criteria:
• Pregnant or breastfeeding as the treatment used in this study are Pregnancy Category D. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
• Active, uncontrolled infection within 1 week prior to starting study therapy
• Malignant solid tumor cancer within previous 2 years Donor Selection (Inclusion Criteria): meets one of the following match criteria:
• an HLA-A, B, DRB1 matched sibling donor (matched sibling)
• an HLA-A, B, DRB1 matched related donor (other than sibling)
• a related donor mismatched at 1 HLA-A, B, C and DRB1 antigen
• 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor per current institutional guidelines Patients and donors are typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. If a donor has been selected on the basis of HLA-A, B, C and DRB1 typing as above, preference will be made for donors matched at the HLA-C locus.
• Body weight of at least 40 kilograms and at least 12 years of age
• Willing and able to undergo mobilized peripheral blood apheresis
• In general good health as determined by the medical provider
• Adequate organ function defined as:
• Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• Hepatic: ALT < 2 x upper limit of normal
• Renal: serum creatinine < 1.8 mg/dl
• Performance of a donor infectious disease screen panel including CMV Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV 1/2 Antibody, HTLVA 1/2 Antibody, Treponema, and Trypanosoma Cruzi (T. Cruzi) plus HBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of and risks factors for infection with Zika virus, or per current standard institutional donor screen - must be negative for HIV and active hepatitis B
• Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
• Voluntary written consent (parent/guardian and minor assent, if < 18 years) prior to the performance of any research related procedure
Drug: Total Body Irradiation (TBI) (Plan 1), Drug: Cyclophosphamide (CY) (Plan 1), Drug: Fludarabine (FLU), Drug: Methylprednisolone (MP), Device: Donor mobilized PBSC infusion, Drug: G-CSF, Drug: Cyclophosphamide (CY) (Plan 2), Drug: Rituximab, Drug: Busulfan
Fanconi Anemia, Severe Aplastic Anemia, Myelodysplastic Syndromes
Clinics and Surgery Center (CSC)
COG AGCT1531 - A Phase 3 Study of Active Surveillance for Low Risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients with Germ Cell Tumors
This partially randomized phase III trial studies how well active surveillance, bleomycin, carboplatin, etoposide, or cisplatin work in treating pediatric and adult patients with germ cell tumors. Active surveillance may help doctors to monitor subjects with low risk germ cell tumors after their tumor is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Emily Greengard
All
Not specified
Phase 3
NCT03067181
STUDY00003824
Inclusion Criteria:
• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patient must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to > 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain at least one of the following: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) < 11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) <
• 0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR
• A serum creatinine based on age/gender as follows: (mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 AND
• Platelet count >= 100,000/mm^3
• Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
Exclusion Criteria:
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >= 1000 ng/mL
• Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
Other: Best Practice, Biological: Bleomycin Sulfate, Drug: Carboplatin, Drug: Cisplatin, Drug: Etoposide, Other: Laboratory Biomarker Analysis, Other: Pharmacogenomic Study, Other: Quality-of-Life Assessment, Other: Questionnaire Administration
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
MT2017-45 :Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients with Hematologic Malignancies
This is a phase II study of FDA-approved CAR-T products for patients with hematologic malignancies. The study provides criteria for consistent treatment and management according to FDA labelling of CAR-T products and does not contain experimental components. Patients will be assigned to Arms A B and C based on age, CAR-T product and diagnosis. Overall remission rate, safety events and other endpoints will be calculated for Arms A B and C separately.
Veronika Bachanova, MD
All
Not specified
Phase 2
NCT03642626
STUDY00004096
ARM A: Kymriah for Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
• Age and Disease Status
• Must be age 0-25 years
• Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
• Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
• Patients with persistent minimal residual disease (MRD >0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
• Patients in 2nd or greater relapse of B-ALL or
• Patients with persistent CNS leukemia, or
• Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
• Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
• Performance Status
• Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening
• ALC >500/uL at screening (prior to apheresis) and absolute lymphocyte count >/= 150/uL
• Organ Function
• Renal function defined as:
• A serum creatinine of ≤1.5 x ULN OR
• eGFR ≥ 50 mL/min/1.73 m2
• Liver function defined as: ** ALT ≤ 5 times the ULN for age (unless due to disease) ** Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤
• 5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Other Inclusion Criteria
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
• CNS 2A
• CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
• Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1 ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma
• Age and Disease Status
• Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
• One of the following histologies and expression of CD19 by tumor cells: ** diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or ** primary mediastinal large B-cell lymphoma, or ** high grade B-cell lymphoma, or ** DLBCL arising from follicular lymphoma
• Disease status: ** Chemotherapy refractory disease after ≥2 lines of chemotherapy, or ** Relapsed with no remission after ≥1 lines of salvage chemotherapy, or ** Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
• Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
• ECOG performance status 0-2
• ALC >/=100/uL at screening (prior to apheresis)
• Renal function defined as: ** A serum creatinine of ≤1.5 x ULN OR ** eGFR ≥ 50 mL/min/1.73 m2
• Liver function defined as:
• ALT ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
• Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
• Platelets ≥ 50.000/mm3 (transfusion support can be provided)
• Hemoglobin >8.0 mg/dl (transfusion support can be provided)
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection (controlled HIV is permissible)
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
• Patient has taken one of the prohibited concomitant medications within the timeframe. ARM C: Kymriah for rRelapsed or rRefractory diffuse large B cell lymphoma
• Age and Disease Status
• Adult patients (age ≥ 18 years)
• with relapsed or refractory (r/r) large B-cell lymphoma, including
• diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
• high grade B-cell lymphoma
• and DLBCL arising from follicular lymphoma.
• Disease status:
• after two or more lines of systemic therapy or
• relapse after autologous HCT
• Performance Status
• ECOG performance status 0-2
• ALC >/=100/uL at screening (prior to apheresis)
• Organ Function
• Renal function defined as:
• A serum creatinine of ≤1.5 x ULN OR
• eGFR ≥ 50 mL/min/1.73 m^2
• Liver function defined as:
• ALT ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
• Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
• Platelets ≥ 50.000/mm3 (transfusion support can be provided)
• Hemoglobin >8.0 mg/dl (transfusion support can be provided)
• Other Inclusion Criteria
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active or inactive HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
• Patient has taken one of the prohibited concomitant medications within the timeframe ARM D: Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell lymphoma
• Age and Disease Status * with relapsed or refractory (r/r) mantle cell lymphoma, including
• prior anthracycline or Bendamustine containing therapy
• prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
• not a candidate or relapse after autologous HCT
• active disease at enrollment
• Performance Status *ECOG performance status 0-1
• Organ Function
• Renal function defined as:
• A serum creatinine of ≤1.5 x ULN OR
• eGFR ≥ 50 mL/min/1.73 m2
• Liver function defined as:
• ALT ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
• Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
• Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
• Hemoglobin >8.0 mg/dl (transfusion support can be provided) Other
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
• Patient has taken one of the prohibited concomitant medications within the timeframe
Inclusion Criteria:
• Age and Disease Status
• Must be age 0-25 years
• Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
• Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
• Patients with persistent minimal residual disease (MRD >0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
• Patients in 2nd or greater relapse of B-ALL or
• Patients with persistent CNS leukemia, or
• Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
• Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
• Performance Status
• Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening
• ALC >500/uL at screening (prior to apheresis) and absolute lymphocyte count >/= 150/uL
• Organ Function
• Renal function defined as:
• A serum creatinine of ≤1.5 x ULN OR
• eGFR ≥ 50 mL/min/1.73 m2
• Liver function defined as: ** ALT ≤ 5 times the ULN for age (unless due to disease) ** Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤
• 5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Other Inclusion Criteria
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
• CNS 2A
• CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
• Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1 ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma
Inclusion Criteria:
• Age and Disease Status
• Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
• One of the following histologies and expression of CD19 by tumor cells: ** diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or ** primary mediastinal large B-cell lymphoma, or ** high grade B-cell lymphoma, or ** DLBCL arising from follicular lymphoma
• Disease status: ** Chemotherapy refractory disease after ≥2 lines of chemotherapy, or ** Relapsed with no remission after ≥1 lines of salvage chemotherapy, or ** Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
• Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
• ECOG performance status 0-2
• ALC >/=100/uL at screening (prior to apheresis)
• Renal function defined as: ** A serum creatinine of ≤1.5 x ULN OR ** eGFR ≥ 50 mL/min/1.73 m2
• Liver function defined as:
• ALT ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
• Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
• Platelets ≥ 50.000/mm3 (transfusion support can be provided)
• Hemoglobin >8.0 mg/dl (transfusion support can be provided)
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection (controlled HIV is permissible)
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
• Patient has taken one of the prohibited concomitant medications within the timeframe. ARM C: Kymriah for rRelapsed or rRefractory diffuse large B cell lymphoma
Inclusion Criteria:
• Age and Disease Status
• Adult patients (age ≥ 18 years)
• with relapsed or refractory (r/r) large B-cell lymphoma, including
• diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
• high grade B-cell lymphoma
• and DLBCL arising from follicular lymphoma.
• Disease status:
• after two or more lines of systemic therapy or
• relapse after autologous HCT
• Performance Status
• ECOG performance status 0-2
• ALC >/=100/uL at screening (prior to apheresis)
• Organ Function
• Renal function defined as:
• A serum creatinine of ≤1.5 x ULN OR
• eGFR ≥ 50 mL/min/1.73 m^2
• Liver function defined as:
• ALT ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
• Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
• Platelets ≥ 50.000/mm3 (transfusion support can be provided)
• Hemoglobin >8.0 mg/dl (transfusion support can be provided)
• Other Inclusion Criteria
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active or inactive HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
• Patient has taken one of the prohibited concomitant medications within the timeframe ARM D: Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell lymphoma
Inclusion Criteria:
• Age and Disease Status * with relapsed or refractory (r/r) mantle cell lymphoma, including
• prior anthracycline or Bendamustine containing therapy
• prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
• not a candidate or relapse after autologous HCT
• active disease at enrollment
• Performance Status *ECOG performance status 0-1
• Organ Function
• Renal function defined as:
• A serum creatinine of ≤1.5 x ULN OR
• eGFR ≥ 50 mL/min/1.73 m2
• Liver function defined as:
• ALT ≤ 5 times the ULN for age (unless due to disease)
• Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
• Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
• Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
• Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
• Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
• Hemoglobin >8.0 mg/dl (transfusion support can be provided) Other
Inclusion Criteria:
• Life expectancy ≥12 weeks
• Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
• Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
• Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
• Uncontrolled active hepatitis B or hepatitis C
• Active HIV infection
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
• Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
• Intolerance to the excipients of the CAR-T cell product
• Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
• Patient has taken one of the prohibited concomitant medications within the timeframe
Drug: KYMRIAH, Drug: YESCARTA, Drug: Fludarabine 30mg/m2 4 doses, Drug: Cyclophosphamide 500 mg/m2, 2 doses, Drug: Fludarabine 30mg/m2 3 doses, Drug: Cyclophosphamide 500 mg/m2, 3 doses, Drug: Fludarabine 25mg/m2 3 days, Drug: Cyclophosphamide 250 mg/m2, 3 days, Drug: Tecartus
Acute Lymphoblastic Leukemia, Large B-cell Lymphoma
ALL, CAR-T, CAR19-T, chimeric antigen receptor T cells, Clinics and Surgery Center (CSC)