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MT2022-41 A Phase 1/2 Study Evaluating the Safety and Efficacy of a Single Dose of Autologous CD34+ Base Edited Hematopoietic Stem Cells (BEAM-101) in Patients with Sickle Cell Disease and Severe Vaso-Occlusive Crises (BEACON Trial) (BEACON)
To determine the safety and clinical efficacy of a single dose of autologous gene--edited CD34+ hematopoietic stem cell and progenitor cells (BEAM-101) in patients with severe SCD
Ashish Gupta
STUDY00017341
Key Inclusion Criteria Include:
Age ≥18 years to ≤35 years for the initial sentinel cohort; for subsequent enrollment patients from ≥12 years up to ≤35 years may be enrolled only upon approval by FDA.
Documented diagnosis of sickle cell disease with βS/βS, βS/β0, or βS/β+ genotypes.
Severe SCD defined by the occurrence of at least 4 severe VOCs in the 24 months prior to screening despite receiving hydroxyurea or other supportive care measures
Key Exclusion Criteria Include:
HbF levels >20%, obtained at the time of screening on or off hydroxyurea therapy
Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation
Available and willing matched sibling donor
Definitive diagnosis of moyamoya syndrome based on screening brain MRA
History of overt stroke
Rare Diseases
Clinics and Surgery Center (CSC)
MT2022-01 Intravenous Administration of Mesenchymal Stem Cells (IV-MSC) for the Treatment of Cerebral Adrenoleukodystrophy (cALD)
The primary objective of this study is to determine the safety of intravenously-administered allogeneic, third-party mesenchymal stem cells (IV-MSC) in patients with active cerebral adrenoleukodystrophy (cALD).
Troy Lund
STUDY00018931
Inclusion Criteria:
• at least 3 years old
• diagnosis of Adrenoleukodystrophy (ALD) by either biochemical or molecular/genetic evidence
• evidence of active cerebral disease (confirmed by MRI within 1 month of the date of enrollment on this study)
• off systemic immunosuppressive drugs (except hydrocortisone and/or fludrocortisone for the treatment of adrenal insufficiency) for at least 10 days before starting the study
• have adequate organ function (study staff will review)
Exclusion Criteria:
• inability to undergo sedation or MRI studies
• other life-threatening disease
Rare Diseases, Cancer
Clinics and Surgery Center (CSC), Childhood Cancer, Adrenoleukodystrophy, ALD
RARE-OB-16: Rare CFTR Mutation Cell Collection Protocol (RARE) (RARE)
We are doing the RARE study to learn more about Cystic Fibrosis (CF). CF is caused by mutations in a gene that produces a protein called the cystic fibrosis transmembrane conductance regulator (CFTR). In people with CF, the CFTR does not function correctly. Medications are being developed to help the CFTR function better, but those medications mostly benefit people with common CFTR mutations. There are more than 1,900 mutations of the CF gene. Some of these mutations are rare and found only in a few people. The goal of this research study is to collect specimens (blood, nasal cells, rectal cells) from people with rare CFTR mutations. Another purpose of this study is to create induced pluripotent stem cells or iPS cells. “Pluripotent” stem cells are cells that can be changed into almost any cell type of the body (such as lung or intestine). They can be kept alive and stored indefinitely. There are different kinds of pluripotent stem cells. Inducted pluripotent stem cells can be created from many different kinds of specimens (such as blood, nasal cells, rectal cells). This is different from embryonic stem cells, which can only be derived from embryos. The specimens collected during this study and iPS cells created from them will be stored for use in future research to learn more about CF and study the effect of new medications. This could identify new medications that may help people with rare CFTR mutations.
Joanne Billings
1702M07621
Inclusion Criteria:
Male or female ≥ 12 years of age at time of consent
Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with CF and one or more of the following criteria (1. Sweat chloride ≥ 60 milliequivalents/Liter (mEq/L) by quantitative pilocarpineiontophoresis test (QPIT) OR upon permission of the RARE Investigator- Sponsors, 2. Two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene, 3.Abnormal nasal potential difference (NPD) (change in NPD in response to a low chloride solution and isoproterenol of lessthan -6.6 mV)
Confirmed genotype of the current recruitment focus for certain target rare mutations. The initial recruitment focus will be CF patients who are homozygous for pre-mature stop codons. Operations Memos will detail any future current genotype targets.
Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability to comply with the requirements of the study.
Willing to travel (if needed) to a regional study site for cell collection.
Exclusion Criteria:
Presence of a medical condition, abnormality, or laboratory value(s) that in the opinion of the onsite principal investigator and/or collaborating gastroenterologist may compromise the quality of the data or place the subject at significant risk by undergoing the research related biopsy, including:
Significantly diseased distal rectal/GI tissue that could place the participant at risk by participating in the study (as judged by the collaborating gastroenterologist, such as significant hemorrhoids, vascular abnormalities, colonic infection, radiation injury or history of radiation therapy to the rectum, prostate and/or pelvic area)
Any of the following abnormal lab values at the study visit:
i. Platelets < 50 x 10^3/µL ii. Hemoglobin < 10 gm/dL iii. Hematocrit < 30% iv. WBC > 20 x 10^3/µL v. Neutropenia (ANC < 1.5 x 10^3/µL) vi. Lymphopenia (absolute lymphocyte count < 1.5 x 10^3/µL) vii. PT/INR > 1.5 viii. Other bleeding diathesis
Positive pregnancy test (for female of childbearing potential) at the study visit.
Breastfeeding (if patient opts to use sedation).
Current use of drugs with significant risks of compromising immunity (e.g. oral steroid use >20 mg/day) for >14 days prior to the rectal biopsy.
History of organ transplant.
Use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such as warfarin or platelet inactivators such as aspirin) within seven days prior to rectal biopsy.
Unable or unwilling to withhold use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such as warfarin or platelet inactivators such as aspirin) within 7 days after rectal biopsy. Clinics and Surgery Center (CSC)
MT2021-29: Evaluation of intravenous laronidase pharmacokinetics before and after hematopoietic cell transplantation in patients with mucopolysaccharidosis type IH
This is a prospective, observational multicenter study to collect blood from patients with mucopolysaccharidosis type IH (MPS-IH) undergoing laronidase therapy and a stem cell transplant.
Silvia Illamola
STUDY00016560
Inclusion Criteria:
Between 0 to 3 years of age
Meet protocol specific eligibility criteria for allogeneic HCT for MPS IH
Planning to receive laronidase both pre and post-transplant in an inpatient setting as part of standard-of-care treatment. Virtually all patients with MPSIH being considered for transplantation at the University of Minnesota are already receiving enzyme infusions, and it is standard practice to continue to give enzyme infusions to 8 weeks post-transplant. Therefore, participation will not modify the treatment course.
Exclusion Criteria:
Patient's parent/ legal guardians are unable to provide informed consent. Rare Diseases
MT2021-01: PTCy + Sirolimus/VIC-1911 as GVHD prophylaxis in myeloablative PBSC transplantation
The primary objective of this study is to determine the optimal dose of VIC-1911 when given in combination with standard immunosuppressive therapy in adult patients undergoing myeloablative stem cell transplantation.
Shernan Holtan
STUDY00015049
Inclusion Criteria:
Diagnosis of
acute leukemia in complete remission, or
myelodysplasia with <5% blasts, or
myeloproliferative neoplasm/myelofibrosis with <5% marrow or circulating blasts
chemosensitive Hodgkin or non-Hodgkin lymphoma
Age 18 years or older
Performance status of ≥ 80% Karnofsky
Adequate organ function within 28 days of study registration defined as:
left ventricular ejection fraction ≥ 45%
pulmonary function with FEV1, FVC, and DLCO ≥ 50% predicted
AST and ALT < 2 times upper limit of normal
Total bilirubin <1.5 times the upper limit of normal. If the patient is suspected of having Gilbert syndrome, they require prior approval of the medical monitor
creatinine clearance ≥ 50cc/min
no active/uncontrolled infection
negative HIV, HBV and HCV
ferritin < 2000 ng/ml
Patients able to tolerate oral medication
Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment through 60 days after the last treatment of VIC-1911 or sirolimus
Able to provide written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
HCT-CI > 4 or unable to receive myeloablative TBI
Use of planned post-transplant maintenance therapy to begin prior to day +75. Patients may receive standard of care maintenance therapies starting at day
+75 or later
Patients with a history of hypersensitivity to any of the investigational products
Pregnant or breastfeeding as agents used in this study are Pregnancy Category
o C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations, and Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 28 days of study registration.
Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 60 days after the last treatment of VIC-1911 or sirolimus Clinics and Surgery Center (CSC)
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
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). Clinics and Surgery Center (CSC)
MT2017-17: Alpha/Beta T Cell Depleted (alpha/beta TCD) Hematopoietic Cell Transplantation in Patients with Fanconi Anemia
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
STUDY00003182
Clinics and Surgery Center (CSC)
MT2014-10C : Allogeneic Hematopoietic Stem Cell Transplant for Patients with High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders
Ashish Gupta
1407M52125
Inclusion Criteria:
Diagnosis of Sickle Cell Disease, Thalassemia, Diamond Blackfan Anemia or other non-malignant hematologic disorders for which a stem cell transplant is indicated
Acceptable stem cell source identified
Performance status of ≥ 70% (Karnofsky),or ≥ 70 (Lansky play score)
Creatinine <2.0 mg/dl for adults or glomerular filtration rate > 50 ml/min for children
Bilirubin, Aspartate Aminotransferase, Alkaline phosphatase <5 times the upper limit of institutional normal
Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%
Exclusion Criteria:
active, uncontrolled infection
pregnant or breastfeeding
HIV positive Clinics and Surgery Center (CSC)
MT2021-03: A Multicenter Randomized Controlled Trial of Best Available Therapy versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (BEAT-MS)
Adam Carpenter
STUDY00007288
Inclusion Criteria:
• active treatment-resistant relapsing MS, defined as at least 2 episodes of disease activity in the past 36 months (study staff will review)
• abnormalities on brain MRI that indicate MS
Exclusion Criteria:
• diagnosis of primary progressive Multiple Sclerosis (MS)
• past or current hepatitis B or hepatitis C infection
• liver disease including cirrhosis
• HIV infection
• active infection of any type
• other medical conditions (study team will review)
Brain & Nervous System, Rare Diseases
Clinics and Surgery Center (CSC), Multiple Sclerosis (MS), relapsing Multiple Sclerosis
MT2013-34C: Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia: Standard of Care Considerations
Christen Ebens
1404M50183
Inclusion Criteria:
Aged 0 - 70 years
Acceptable hematopoeitic stem cell donor
Dyskeratosis Congenita (DC) with evidence of BM failure defined as:
requirement for red blood cell and/or platelet transfusions or
requirement for G-CSF or GM-CSF or erythropoietin or
refractory cytopenias having one of the following three
platelets <50,000/uL or transfusion dependent
absolute neutrophil count <500/uL without hematopoietic growth factor support
hemoglobin <9g/uL or transfusion dependent
Diagnosis of DC with a triad of mucocutaneous features:
oral leukoplakia
nail dystrophy
abnormal reticular skin hyperpigmentation, or
Diagnosis of DC with one of the following:
short telomeres (under a research study)
mutation in telomerase holoenzyme (DKC1, TERT, TERC, NOP10, NHP2, TCAB1)
mutation in shelterin complex (TINF2)
mutation in telomere-capping complex (CTC1)
Severe Aplastic Anemia (SAA) primary transplant with evidence of BM failure:
Refractory cytopenia defined by bone marrow cellularity <50% (with < 30% residual hematopoietic cells)
Diagnosis of SAA with refractory cytopenias having one of the following three:
platelets <20,000/uL or transfusion dependent
absolute neutrophil count <500/uL without hematopoietic growth factor support
absolute reticulocyte count <20,000/uL
Severe Aplastic Anemia (SAA) requiring a 2nd transplant
Graft failure as defined by blood/marrow chimerism of < 5%
Early myelodysplastic features
With or without clonal cytogenetic abnormalities
Adequate organ function defined as:
cardiac: left ventricular ejection fraction ≥ 35% with no evidence of decompensated heart failure
pulmonary: DLCO ≥30% predicted, no supplemental oxygen requirement
renal: Glomerular filtration rate (GFR) ≥30% predicted
Voluntary written consent
Exclusion Criteria:
Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
Pregnant or lactating
Uncontrolled infection
Prior radiation therapy (applies to SAA patients only)
Diagnosis of Fanconi anemia based on DEB
Diagnosis of dyskeratosis congenita with advanced MDS or acute myeloid leukemia with >30% blasts 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
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).MT2013-06C : Treatment of graft Failure after HSCT
Troy Lund
1404M49341
Inclusion Criteria:
Patients with primary or secondary graft failure, as defined below, may receive a second transplant:
Primary graft failure is defined as not achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42 following the first transplant.
Secondary graft failure is defined as achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10^9/L without recovery.
Loss of chimerism is defined as achieving an ANC ≥0.5x10^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood.
Recipients should have acceptable organ function defined as:
Renal: creatinine < 2.0 (adults) and creatinine clearance > 30. For creatinine clearance < 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments.
Hepatic: bilirubin, AST/ALT, ALP < 10 x upper limit of normal
Cardiac: left ventricular ejection fraction > 40%
Exclusion Criteria:
Uncontrolled infection at the time of transplant.
Patients with Fanconi Anemia or other DNA breakage syndromes. Clinics and Surgery Center (CSC)
MT2012-10C: Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Christen Ebens
1207M17321
Inclusion Criteria:
Diagnosis of immunodeficiency or histiocytic disorder including the following:
Severe combined immunodeficiency (SCID - all variants)
Second bone marrow transplant (BMT) for SCID (after graft rejection)
Omenn's Syndrome
Reticular dysgenesis
Wiskott-Aldrich syndrome
Major histocompatibility complex (MHC) Class II deficiency (bare lymphocyte syndrome)
Hyper IgM Syndrome (CD40 Ligand Deficiency)
Common variable immunodeficiency (CVID) with severe phenotype
Chronic Granulomatous Disease (CGD)
Other severe Combined Immune Deficiencies (CID)
Hemophagocytic Lymphohistiocytosis (HLH)
X-linked Lymphoproliferative Disease (XLP)
Chediak-Higashi Syndrome (CHS)
Griscelli Syndrome
Langerhans Cell Histiocytosis (LCH)
Acceptable stem cell sources include:
HLA identical or 1 antigen matched sibling donor eligible to donate bone marrow
HLA identical or up to a 1 antigen mismatched unrelated BM donor
Sibling donor cord blood with acceptable HLA match and cell dose as per current institutional standards
Single unrelated umbilical cord blood unit with 0-2 antigen mismatch and minimum cell dose of >5 x 10^7 nucleated cells/kg as per current institutional guidelines
Double unrelated umbilical cord blood units that are:
up to 2 antigen mismatched to the patient
up to 2 antigen mismatched to each other
minimum cell dose of at least one single unit must be ≥ 3.5 x 10^7 nucleated cells/kg
combined dose of both units must provide a total cell dose of ≥ 5 x 10^7 nucleated cells/kg
Age: 0 to 50 years
Adequate organ function and performance status.
Exclusion Criteria
pregnant or breastfeeding
active, uncontrolled infection and/or HIV positive
acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy 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
Shernan Holtan
STUDY00001087
-
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. Clinics and Surgery Center (CSC)
MT2012-11C: Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)
This is a treatment guideline for a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of busulfan, fludarabine, and low dose total body irradiation (TBI), is designed to promote engraftment in patients who failed to achieve an acceptable level of donor-derived engraftment following a previous allogeneic HSCT. While it will primarily be applied for the treatment of non-malignant diseases (NMD), on occasion it may be used to treat patients with malignant disorders as well.
Troy Lund
1207M17641
Inclusion Criteria:
Diagnosis of any disease for which a second or greater hematopoietic stem cell transplant is needed due to insufficient donor chimerism following hematopoietic recovery after previous HSCT. Determination of "insufficiency of donor chimerism" will be made by the treating transplant physician. Occasionally donor derived engraftment may be present, but sustained aplasia or failed recovery of sufficient hematopoiesis requires administration of a second graft. This intervention may be used for both situations.
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
Transplantation using sufficiently matched related donors (such as matched siblings) or unrelated donors will be considered. Both granulocyte-colony stimulating factor (GCSF) stimulated peripheral blood grafts and bone marrow grafts will be considered, although bone marrow will be the priority.
Cord blood grafts, both related and unrelated, are also eligible. As this protocol will use a reduced intensity regimen, this protocol will use the current recommendations of the University of Minnesota for choosing cord blood grafts. If a single cord blood unit cell dose is insufficient, double cord transplantation should be considered if sufficiently matched cord blood units are available. The priority of choosing cord blood donors is based on the current institutional recommendations.
Exclusion of Metabolic Disorder or other Inherited Disorder Carrier Status from related donor and unrelated cord blood grafts as appropriate for primary disease.
At the discretion of the treating transplant physician, an allograft from the previous donor may be used, if available.
Age, Performance Status, Consent
Age: 0 to 55 years
Consent: voluntary written consent (adult or parental/guardian)
Exclusion Criteria:
Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI). Radiation Oncology will evaluate all patients who have had previous radiation therapy or TBI for approval to receive an additional 200 cGy of TBI
Pregnant or breastfeeding
Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted
HIV positive
While it would be advantageous to begin therapy on this second transplant regimen > 6 months following a prior myeloablative regimen or >2 months after a reduced intensity regimen, it is recognized that there are circumstances where this may not be practical.MT2015-25: Tandem Myeloablative Consolidation Therapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
Ashish Gupta
1601M82901
Less than 30 years of age at diagnosis of neuroblastoma
End of Induction disease evaluation demonstrating CR, PR, MR or SD
Hematopoietic Recovery from last induction course of chemotherapy
No uncontrolled infection
Minimum frozen PBSCs of 2 x 10^6 CD34 cells/kg for each transplant are mandatory and a PBSC of 2 x 10^6 CD34 cells/kg for back-up are strongly recommended (thus, PBSC of no less than 6 x 10^6 CD34 cells/kg is encouraged). These must all be collected prior to the initiation of consolidation.
Adequate organ function defined as:
Hepatic: AST and ALT < 3 x upper limit of institutional normal; ALT ≤ 3 x ULN for age; total bilirubin ≤ 1.5 x ULN for age, if baseline was normal, > 1.0 1.5 x baseline if baseline was abnormal
Cardiac: shortening fraction ≥ 27% or ejection fraction ≥ 45%, no clinical congestive heart failure
Pulmonary: no evidence of dyspnea at rest and norequirement for supplemental oxygen
Renal: Creatinine clearance or GFR > 60 mL/min/1.73m^2. If a creatinine clearance is performed at end induction and the result is < 100 ml/min/1.73m^2, a GFR must then 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/1.73m^2
Recovery from acute toxicities of last cycle of induction chemotherapy
Appropriate written consent - adult or parent/guardian if patient is < 18 years of age and minor information sheet if patient is > 8 years of age
MT2021-08: Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults with Hematological Malignancies
Margaret MacMillan, MD
STUDY00016450
Inclusion Criteria:
• hematological cancer needing stem cell transplant
• 60 years old or younger
Exclusion Criteria:
• pregnant or breast feeding
• active infection
• positive for HIV, Hepatitis B or C
• brain metastasis
Cancer
Blood Cancers, Hematologic Malignancy, Leukemia, Stem Cell Transplant, 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
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 Clinics and Surgery Center (CSC)
MT2019-06: A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the LentiGlobin BB305 Lentiviral Vector in Subjects with Sickle Cell Disease.
Evaluate the efficacy of treatment with bb1111 (also known as LentiGlobin BB305 Drug Product for Sickle Cell Disease) in subjects with sickle cell disease (SCD).
Ashish Gupta
STUDY00006923
Inclusion Criteria:
Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
Be ≥2 and ≤50 years of age at time of consent.
Weigh a minimum of 6 kg.
Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
In the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent.
Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
Female and male subjects of childbearing potential agree to use 1 method of highly effective contraception from Screening to at least 6 months after drug product infusion.
Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s).
Exclusion Criteria:
Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity >200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity > 200 cm/sec (central read), a Screening MRA showing > 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
Clinically significant, active bacterial, viral, fungal, or parasitic infection
Advanced liver disease, such as
clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
Inadequate bone marrow function, as defined by an absolute neutrophil count of <1×10^9/L (<0.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count <100×10^9/L.
Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
Unable to receive pRBC transfusion.
Prior receipt of an allogeneic transplant.
Prior receipt of gene therapy.
Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
Immediate family member with a known or suspected Familial Cancer Syndrome.
Female subject is breastfeeding, pregnant or will attempt to become pregnant from Screening to at least 6 months after drug product infusion.
Any other condition that would render the subject ineligible for HSCT.
Participation in another clinical study with an investigational drug within 30 days of screening.
Presence of a chromosomal abnormality or genetic mutation that may put the subject at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) per Investigator's judgment.
Presence of genetic mutations that result in the inactivation of 2 or more α-globin genesMT2021-36: A Randomized, Open Label Phase 3 Study Evaluating Safety and Efficacy of Venetoclax in combination with Azacitidine after allogeneic Stem Cell Transplantation in Subjects with Acute Myeloid Leukemia (AML) (VIALE-T) (VIALE-T)
Part 1 Primary: To determine the recommended Phase 3 dose of venetoclax in combination with azacitidine in AML subjects when given as maintenance therapy following allogeneic SCT. Part 2 primary: 1. To determine the efficacy of venetoclax in combination with azacitidine to improve RFS in AML subjects compared to BSC when given as maintenance therapy following allogeneic SCT
Mark Juckett
STUDY00014681
Inclusion Criteria:
Participants must be at least 18 years old for Part 1 and, at least 12 years old for Part 2.
Participant must be diagnosed with Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell transplantation or have received allogeneic stem cell transplantation within the past 60 days.
Blast percentage in bone marrow before transplant must be < 10%.
Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must be < 5% after transplant.
Participant meet adequate renal, hepatic and hematologic criteria as described in the protocol.
Participants >= 17 years old must have a Karnofsky Performance Scale (KPS) score > 50 and participants between 12 to 16 years old must have a Lansky Play Performance Scale score > 40.
Exclusion Criteria:
History of disease progression during prior treatment with venetoclax.
History of any other malignancy within 2 years prior to study entry, except for: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; Myelodysplastic Syndrome, Myeloproliferative neoplasm (only allowed if it transformed to AML and AML should be the indication for marrow transplantation).
Participant has known infection with HIV or history of being positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
Presence of clinical or laboratory symptoms/signs of extramedullary myeloid malignancy. Clinics and Surgery Center (CSC)
MT2021-27 Intraperitoneal FT538 with Intravenous Enoblituzumab in Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
This is a Phase I, single center study to evaluate the treatment of FT538 administered intraperitoneally (IP) and in combination with intravenous (IV) enoblituzumab once a week for three consecutive weeks for the treatment of recurrent ovarian, fallopian tube, and primary peritoneal cancer. This is an early first in human and first intraperitoneal (IP) infusion of FT538, and safety is confirmed prior to the addition of intravenous (IV) enoblituzumab. FT538 is an allogeneic natural killer (NK)-cell immunotherapy produced from a clonal master human-induced pluripotent stem cell (iPSC) line with the following engineered elements: a) deletion of the gene encoding CD38 (i.e., CD38 knockout); b) high-affinity, non-cleavable CD16 receptor and c) interleukin (IL)-15/IL-15 receptor alpha fusion protein. Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3 which is highly expressed on ovarian cancer. Enoblituzumab is given on Day-6 prior to the 1st dose of FT538 and every 3 weeks beginning on Day 22 until disease progression or unacceptable toxicity. A short course of outpatient lymphodepleting chemotherapy is given before the 1st dose of FT538, but after the 1st enoblituzumab infusion for patients assigned to Dose Cohort 5 or Dose Cohort 6.
Melissa Geller, MD
STUDY00016513
Inclusion Criteria:
• recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer
• oxygen saturation at least 90% without oxygen therapy
• no significant history of heart disease
Exclusion Criteria:
• pregnant or breastfeeding
• receiving immunotherapy for cancer treatment
• active autoimmune disease
Cancer, Women's Health
Fallopian tube cancer, Ovarian cancer, Peritoneal cancer, 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
Christopher Moertel, MD
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.MT2013-31:Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis following Conditioning with Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
To evaluate the ability to achieve high-level donor hematopoietic engraftment (defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant) using related and unrelated BM, PBSC, or UCB grafts following a reduced intensity conditioning regimen based on targeted-exposure busulfan, fludarabine +/- serotherapy in patients with inherited metabolic disorders and severe osteopetrosis.
Paul Orchard
1406M51542
Inclusion Criteria:
0 through 55 years of age
Adequate graft available
Adequate organ function
Eligible Diseases:
Mucopolysaccharidosis Disorders:
MPS IH (Hurler syndrome)
MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
MPS VI (Maroteaux-Lamy syndrome)
MPS VII (Sly syndrome)
Glycoprotein Metabolic Disorders:
Alpha mannosidosis
Fucosidosis
Aspartylglucosaminuria
Sphingolipidoses and Recessive Leukodystrophies:
Globoid cell leukodystrophy
Metachromatic leukodystrophy
Niemann-Pick B patients (sphingomyelin deficiency)
Niemann-Pick C subtype 2
Peroxisomal Disorders:
Adrenoleukodystrophy with cerebral involvement
Zellweger syndrome
Neonatal Adrenoleukodystrophy
Infantile Refsum disease
Acyl-CoA-Oxidase Deficiency
D-Bifunctional enzyme deficiency
Multifunctional enzyme deficiency
Alpha-methylacyl-CoA Racmase Deficiency (AMACRD)
Mitochondrial Neurogastrointestingal Encephalopathy (MNGIE)
Severe Osteopetrosis (OP)
Hereditary Leukoencephalopathy with axonal spheroids (HDLS; CSF1R mutation)
Other Inherited Metabolic Disorders (IMD): Patients will also be considered who have other life-threatening, rare lysosomal, peroxisomal or other similar inherited disorders characterized by white matter disease or other neurologic manifestations for which there is rationale that transplantation would be of benefit, such as certain patients with Wolman's disease, GM1 gangliosidosis, I-cell disease, Tay-Sachs disease, Sandhoff disease or others.
Voluntary written consent
Exclusion Criteria:
Pregnancy - menstruating females must have a negative serum or urine pregnancy test within 14 days of study treatment start
Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol (patients excluded for this reason may be eligible for other institutional protocols)
Uncontrolled bacterial, fungal or viral infections including HIV (including active infection with Aspergillus or other mold within 30 days) Clinics and Surgery Center (CSC)
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
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 participationMT-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
STUDY00003635
Inclusion Criteria:
For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled
For patients who have not previously enrolled on APEC14B1 prior to enrollment on AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an MRD probe
In addition, laboratory reports detailing evidence of BCR-ABL1 fusion or ABL-class fusion must be submitted for rapid central review within 72 hours of study enrollment
>= 1 year (365 days) and =< 21 years at ALL diagnosis
Ph+ (BCR-ABL1 fusion): newly diagnosed de novo 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 molecular methodologies
ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA. 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 (e.g. TruSight RNA Pan-Cancer Panel; Illumina, San Diego, CA, USA or similar)
Ph+ patients must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
Ph+ patients have not received more than 14 days of multiagent Induction therapy beginning with the first dose of vinCRIStine
Ph+ 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 (Induction IA phase)
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 other than imatinibMT2020-35 - COG AAML1831 - A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations
The overall goal of this study is to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, and to find out what effects, good and/or bad, the drug gilteritinib has when given with chemotherapy to children and young adults with newly diagnosed AML and the FLT3/ITD mutation or non-ITD FLT3 activating mutations.
Peter Gordon
STUDY00010751
Inclusion Criteria:
All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures
Patients must be less than 22 years of age at the time of study enrollment
Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
Patient must have 1 of the following:
>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
ARM C: Patient must be >= 2 years of age at the time of Late Callback
ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology
ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
ARM D: Patient must be >= 2 years of age at the time of Late Callback
ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
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:
Fanconi anemia
Shwachman Diamond syndrome
Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
Telomere disorders
Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
Any concurrent malignancy
Juvenile myelomonocytic leukemia (JMML)
Philadelphia chromosome positive AML
Mixed phenotype acute leukemia
Acute promyelocytic leukemia
Acute myeloid leukemia arising from myelodysplasia
Therapy-related myeloid neoplasms
Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) < 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
Administration of prior anti-cancer therapy except as outlined below:
Hydroxyurea
All-trans retinoic acid (ATRA)
Corticosteroids (any route)
Intrathecal therapy given at diagnosis
In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
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
ARM D: Patient does not have any congenital long QT syndrome or congenital heart block