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National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) - A Collaborative Initiative to Improve Care of Children with Complex Congenital Heart Disease (NPC-QIC)
Kavisha Shah
Up to 18 years old
STUDY00004329
Inclusion Criteria:
• up to 15 months old
• newborns diagnosed with HLHS or other univentricular condition
• intended to undergo Norwood procedure
Children's Health, Heart & Vascular
Hypoplastic Left Heart Syndrome (HLHS)
Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training in MCI (The ACT Trial)
Dereck Salisbury
18 years and over
STUDY00001135
Inclusion Criteria:
-65 years and older
• diagnosis of Mild Cognitive Impairment
• live in the community
• English speaking
• adequate vision
• physician confirms that exercise is safe
• stable on drugs affecting cognitive and psychological status
• able to have a MRI
Exclusion Criteria:
• resting heart rate less than 50 or greater than 100
• additional medical or mental health diagnosis (study staff will review)
• enrolled in another intervention study related to cognitive improvement
Brain & Nervous System, Community Health
cognitive decline, memory complaint, mild cognitive impairment
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
Up to 25 years old
SITE00000151
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 APEC14B1Clinical Study of the BioVentrix Revivent TC System for Treatment of Left Ventricular Aneurysms
The Revivent TC System study is being conducted to test an investigational device that can repair a Left Ventricular Aneurysm without the use of a heart-lung machine, or opening the chest/heart chamber. The device works by placing a tuck in the heart where there is scar. This has the effect of shortening the distance across the heart and decreasing the stress on the working heart muscle. Follow up will last for 5 years after the device is placed.
Tamas Alexy
18 years and over
1703M11122
Inclusion Criteria:
• 18 to 100 years old
• diagnosis of LV Aneurysm or scar
• Left Ventricular Ejection Fraction less than 45%
• symptoms of heart failure that aren't improving with treatment
• for people in the comparison group: have had previous pericardiotomy, left thoracotomy, or open heart surgery OR the location of the LV aneurysm or scar does not permit treatment with the study device
Exclusion Criteria:
• valvular heart disease which will require surgery
• contact study staff for additional criteria
Heart & Vascular
Clinics and Surgery Center (CSC), Left Ventricular Dysfunction. Left Ventricular Aneurysm
MT2015-29 : Myeloablative Allogeneic Hematopoietic Cell Transplantation Using a Related or Adult Unrelated Donor for the Treatment of Hematological Disorders
Shernan Holtan
Up to 60 years old
STUDY00001087
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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)
Neoadjuvant therapy for patients with high risk stage III melanoma: a pilot clinical trial (NeoACTIVATE)
The purpose of this research is to see if neoadjuvant therapy (treatment given before surgery) with the combination of atezolizumab and tiragolumab is safe and effective for treating newly diagnosed advanced stage melanoma. In addition, we are looking at how atezolizumab given as adjuvant therapy (treatment after the tumor is surgically removed) works to prevent recurrence of melanoma.
Evidio Domingo Musibay
18 years and over
STUDY00004666
Inclusion Criteria:
• diagnosis of High-risk stage III melanoma
• disease that can be surgically removed, (determined by a melanoma surgical oncologist)
• willing to use highly effective birth control for six months after treatment is stopped
• physically able to care for self and do light work activities
• willing to delay starting cancer treatment until study requirements are completed
• contact study staff for additional requirements
Exclusion Criteria:
• prior systemic anti-cancer therapy for melanoma
• prior radiotherapy for melanoma
• other cancer diagnosis less than 3 years ago
• other medical and mental health diagnosis that would interfere with treatment (study staff will review)
• women who are pregnant or breast feeding
Cancer
Clinics and Surgery Center (CSC), Melanoma
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
1 year to 21 years old
SITE00000271
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 imatinibCOG 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
Up to 30 years old
SITE00000284
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 treatmentCOG 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
3 years to 21 years old
SITE00000161
Inclusion Criteria:
Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment
Patients must be newly diagnosed and have:
Eligibility confirmed by rapid central pathology and molecular screening review on APEC14B1 and via the Molecular Characterization Initiative:
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 >= 8.0 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. Children with posterior fossa syndrome (also known as cerebellar mutism) are eligible for this studyAn Open Label Study to Evaluate DPCP Ointment for the Treatment of Alopecia Areata
The purpose of the study is two-fold. First, we will see whether treating alopecia areata with a ointment containing DPCP is safe and causes hair to regrow. Second, we will take blood and scalp biopsy samples and analyze them for biomarkers. The biomarkers in this study are molecules related to DNA that tell us whether certain genes are turned on or off. Those markers may help us predict whether or not patients respond to this type of treatment. The testing for biomarkers will also help us to better understand what causes alopecia areata. This study requires you to make forty-two (42) visits to the study site over a course of approximately four (4) months.
Maria Hordinsky
18 years and over
1407M52002
Inclusion Criteria:
• diagnosis of extensive alopecia areata
• women of childbearing age must agree to use an acceptable, highly effective method of birth control to prevent pregnancy
Exclusion Criteria:
• women who are pregnant or breast feeding
• current controlled or uncontrolled infection of any type
• systemic therapy for cancer within the past five years except for adequately treated Squamous Cell Carcinoma (SCC) or Basal Cell Carcinoma (BCC) of the skin
• additional medical conditions, treatments for alopecia areata, or mental health diagnosis (study staff will review)
Dermatology (Skin, Hair & Nails)
Alopecia Areata
Vertical Sleeve Gastrectomy and Lifestyle Modification for the Treatment of Non-Alcoholic Steatohepatitis
This study is comparing the treatment of Non-Alcoholic Steatohepatitis (NASH) with either lifestyle changes or obesity surgery with lifestyle changes. Participants must be 30-70 years old, have a BMI of 35.0-60.0 kg/m2, have health insurance that will pay for obesity surgery, and be willing to accept either treatment.
Sayeed Ikramuddin
18 years and over
STUDY00014879
Inclusion Criteria:
• ages 30 to 70 years
• diagnosed with NASH with a total NAS >=4 including a ballooning score of at least 1, or diagnosed with T2DM or prediabetes, HbA1c < 9% Body Mass Index (BMI): 35.0-50.0 kg/m2
• willing to accept either surgery or life style changes
• must have insurance with no exclusion for obesity related treatments or management of obesity surgery complications. applies to all participants enrolled in the study
• evidence of liver fat present in the baseline MR images
• suitable for liver biopsy
Exclusion Criteria:
• cardiovascular event (myocardial infarction, acute coronary syndrome, coronary artery angioplasty or bypass, stroke) in the past six months
• pulmonary embolus or thrombophlebitis in the past six months
• cancer diagnosis unless disease free for five years
• alcohol intake more than one drink per day
• other physical or mental health disease (study staff will review)
Digestive & Liver Health
Bariatric Surgery, NASH, VSG, 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)
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
SITE00000295
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) < 3.0 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 (within 7 days prior to enrollment) OR
A serum creatinine based on age/gender as follows (within 7 days prior to enrollment): (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 (within 7 days prior to enrollment)
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) (within 7 days prior to enrollment)
Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to enrollment) AND
Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
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])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
STUDY00004096
ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
Inclusion Criteria:
Age and Disease Status
Must be age 0-25 years (for Arm A Kymriah) or >18 years (Arm G Tecartus)
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
* Arm A: Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
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
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
ARM E: Breyanzi "lisocabtagene maraleucel" for relapsed or refractory large B-cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
with relapsed or refractory disease after two or more lines of systemic therapy, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma),
high-grade B-cell lymphoma,
primary mediastinal large B-cell lymphoma,
follicular lymphoma grade 3B
Performance Status
*ECOG performance status 0-2
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 30 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 ≥ 40% 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
ARM F: Abecma "Idecabtagene Vicleucel" for relapsed or refractory multiple myeloma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
Relapsed (progression after prior partial or complete remission) or refractory multiple myeloma
Evidence of active disease (medullary or extramedullary)
Prior therapy (Failure or intolerance to) with an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody
Performance Status
*ECOG performance status 0-1
Organ Function
Renal function defined as:
A serum creatinine of ≤2 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 Clinics and Surgery Center (CSC)
The Organ Care System (OCS) Lung Thoracic Organ Perfusion (TOP) Post Approval Study (PAS) Registry - OCS Lung TOP PAS Registry (TOP)
To collect additional real-world safety and effectiveness data for the OCS™ Lung System and to expand the long-term clinical evidence supporting the use of OCS™Lung System in lung transplantation.
Stephen Huddleston
18 years and over
STUDY00003837
Inclusion Criteria:
• people who received OCS preserved double lung transplants
• OR people who receive a single lung transplant from OCS preserved lung pairs from either standard criteria donors
• AND all donor lungs that were perfused on OCS Lung System
Brain & Nervous System
Clinics and Surgery Center (CSC), Lung Transplant
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
18 years and over
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
Phase 1/2 Study to Evaluate Palbociclib (IBRANCE?) in Combination With Irinotecan and Temozolomide or in Combination with Topotecan and Cyclophosphamide in Pediatric Patients With Recurrent or Refractory Solid Tumors Protocol No.: ADVL1921/A5481092
This is a Phase 1/2 multicenter, open-label study to evaluate palbociclib in combination with either irinotecan (IRN) and temozolomide (TMZ) or topotecan (TOPO) and cyclophosphamide (CTX) chemotherapy in children, adolescents and young adults with recurrent or refractory solid tumors. The study consists of a non- randomized Phase 1 portion for recurrent or refractory solid tumors followed by potential non- randomized tumor specific cohort(s) and a randomized, Phase 2 portion for recurrent or refractory EWS.
Emily Greengard
2 years to 20 years old
STUDY00007068
Inclusion:
Histologically confirmed relapsed or refractory solid tumor as follows:
For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
Age ≥2 and <21 years at the time of study entry.
Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
Adequate bone marrow function.
Absolute neutrophil count ≥1000/mm3;
Platelet count ≥75,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
Hemoglobin ≥8.5 g/dL (transfusion allowed).
Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
Adequate liver function, including:
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.Patients with documented Gilbert's syndrome are eligible if direct bilirubin is within normal ranges (≤ULN).
Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or at least evaluable disease by INRC for neuroblastoma.
The eligible patients with neuroblastoma must have at least one of the following at the time of study entry:
Measurable tumor by CT or MRI that is avid on MIBG scan or demonstrates increased FDG uptake on PET scan;
Avid lesion on MIBG scan with positive uptake at a minimum of one site;
For disease that is not avid by MIBG-scan, at least one lesion that demonstrates increased FDG uptake on PET scan AND viable neuroblastoma confirmed by current or prior biopsy;
bone marrow involvement with more than 5% neuroblastoma cells in at least one sample from bilateral bone marrow biopsies;
In non MIBG-avid refractory soft tissue disease that does not demonstrate increased FDG uptake; lesion biopsy is required to document the presence of viable neuroblastoma, unless patient has a new soft tissue lesion (radiographic evidence of disease progression).
Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
Exclusion:
Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. For patients enrolled in the UK, any contraindication for IRN and/or TMZ treatment, as per the local SmPC.
Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers within 12 days of study entry. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
Prior irradiation to >50% of the bone marrow (see Appendix 9).
Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, dacarbazine, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
Hereditary bone marrow failure disorder.
QTc >470 msec.
History of clinically significant or uncontrolled cardiac disease, including:
History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
Diagnosed or suspected congenital or acquired prolonged QT syndrome;
Need for medications known to prolong the QT interval;
Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
Left ventricular ejection fraction <50% or shortening fraction <28%.
Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. Screening for viral hepatitis and HIV is under discretion of investigator unless required by local regulation.
Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
Fertile male patients or female patients of childbearing potential who are unwilling or unable to follow contraceptive requirements.
Pregnant or breastfeeding women.
MT2019-38: Development and Psychometric Testing of a Pediatric Chronic Graft-Versus-Host Disease (GVHD) Symptom Scale (PCSS)
To develop a psychometrically valid Pediatric cGVHD Symptom Scale (PCSS) and a companion parent-proxy measure as counterparts to the Lee cGVHD Symptom Scale.
Margaret MacMillan, MD
5 years and over
SITE00000722
INCLUSION CRITERIA:
Pediatric Subject
Inclusion Criteria:
Children aged 5 to 17 years old, who have undergone prior allogeneic stem cell transplant
Clinical diagnosis of cGVHD
Currently receiving systemic treatment for cGVHD (including phototherapies), or has had systemic therapy for cGVHD tapered to discontinuation within the past 12 months
No evidence of malignant disease relapse including molecular relapse and minimal residual disease. Patients with mixed chimerism are eligible to participate
Subject must have an eligible caregiver proxy who is willing to participate in the study.
Parent or guardian ability and willingness to sign a written informed consent document
Subjects must be able to comprehend and speak the English language
Subjects may participate in both Project 1 and Project 2 of the study. Participation in Project 1 is not required in order to be eligible to participate in Project 2.
Caregiver Proxy Inclusion Criteria
Adult, >18 years of age, caregiver of participating subject
Must be willing and able to provide informed consent.
Must be able to comprehend and speak the English language
EXCLUSOIN CRITERIA:
Patients may be excluded from this study if in the judgment of the Principal or Associate Investigator, the subject is too ill, or subject s cognitive ability would compromise their ability to participate in study related procedures.Enhanced Spatial Targeting in ECT Utilizing Focally Electrically-administered Seizure Therapy (FEAST)
The purpose of this study is to look at a different type of electroconvulsive therapy (ECT) that may reduce negative side effects while still providing relief from symptoms of major depression.
Ziad Nahas
18 years and over
STUDY00006734
Inclusion Criteria:
• age 22 to 90
• diagnosis of major depression
• ECT recommended for treatment
Exclusion Criteria:
• other psychiatric diagnosis such as schizophrenia, schizoaffective disorder, other psychosis
• history of neurological illness -alcohol or substance abuse or dependence in the past year
• ECT in the past six months
Mental Health & Addiction
depression, ECT, Electroconvulsive therapy (ECT), major depressive disorder
PRI-VENT FSGS: Preemptive Rituximab to Prevent Recurrent Focal Segmental Glomerulosclerosis Post-Transplant
We are testing whether treating people who have FSGS with plasmapheresis and rituximab before or shortly after kidney transplant can prevent the recurrence of FSGS after the kidney transplant. All participants will receive plasmapheresis. Each participant has a 50% chance of receiving rituximab and a 50% chance of receiving no additional treatment. Rituximab is given by infusion. If a participant is assigned to receive rituximab, your child will receive it one time immediately after the plasmapheresis session.
Michelle Rheault
1 year to 65 years old
STUDY00004388
Inclusion Criteria:
• 1 to 65 years old
• biopsy proven diagnosis of primary focal segmental glomerulosclerosis (FSGS) or minimal change disease
• history of nephrotic syndrome (proteinuria, edema, hypoalbuminemia)
• first kidney transplant or second or third transplant with a history of recurrent FSGS in the first or second kidney transplant
• males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment with rituximab
Exclusion Criteria:
• known genetic cause of FSGS
• FSGS secondary to another condition (obesity, viral infection, medications, etc.)
• received rituximab within 1 year prior to transplant
• women who are pregnant, lactating, or refuse use of birth control
• additional medical or mental health diagnosis (study staff will review)
Kidney, Prostate & Urinary
Focal Segmental Glomerulosclerosis
COG AALL1731 - A Phase 3 Trial Investigating Blinatumomab (IND# 117467, NSC# 765986) in Combination with Chemotherapy in Patients with Newly Diagnosed Standard Risk or Down syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients with Localized B-Lymphoblastic Lymphoma (B-LLy)
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients (365 Days to 31 Years) with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, 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. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better then combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.
Peter Gordon
365 days to 31 years old
SITE00000644
Inclusion Criteria:
All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
Age at diagnosis:
Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;
OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
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:
Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
For patients receiving steroid pretreatment, the following additional exclusion criteria apply:
Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to the start of systemic protocol therapy.
B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
Patient must not have acute undifferentiated leukemia (AUL).
Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).
Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
For LLy patients, the following additional exclusion criteria apply:
T-Lymphoblastic Lymphoma.
Morphologically unclassifiable lymphoma.
Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
CNS positive disease or testicular involvement.
M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
Patients with known Charcot-Marie-Tooth disease.
Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
Patients requiring radiation at diagnosis.
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.SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) Trial (SHARP)
We are studying the effectiveness of a new procedure to treat people who have episodes of acute pancreatitis with pancreas divisum. Of the participants, half will receive the new procedure called endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic spincterotomy (miES) the other half with receive only ERCP. We will monitor outcomes for at least eighteen months.
Martin Freeman
18 years and over
SITE00000387
Inclusion Criteria:
• at least 18 years old
• two or more episodes of acute pancreatitis, with one occurring in the last 24 months
• there is no certain explanation for recurrent acute pancreatitis
Exclusion Criteria:
• prior minor papilla therapy (endoscopic or surgical)
• other causes of pancreatitis (study staff will review)
• regular use of opioid medication for abdominal pain for the past three months
Digestive & Liver Health
Clinics and Surgery Center (CSC), ERCP, Pancreatitis
Phase II trial of androgen deprivation therapy (ADT) and pembrolizumab for advanced stage androgen receptor-positive salivary gland carcinoma: Big Ten Cancer Research Consortium BTCRC-HN17-111
We are looking at the effectiveness of adding an immunotherapy drug, pembrolizumab, to usual treatment for people who have salivary gland cancer that can’t be treated with surgery or radiation. The cancer must be androgen receptor positive.
Manish Patel
18 years and over
STUDY00004710
Inclusion Criteria:
• at least 18 years old
• locally advanced, recurrent, or metastatic salivary gland carcinoma that is not amenable to curative surgery or radiation
• tumor is androgen receptor-positive
• unable to do physically strenuous activity but can walk and is able to do work of a light nature, such as house work or office work
• prior chemotherapy, radiation, or surgery as part of curative intent therapy are allowed
• any number of prior lines of systemic therapy are permitted as long as it did not include anti-androgen therapy or immune checkpoint blockade
• men and women of child bearing age must agree to use contraception during the treatment period and for at least 8 months after the last dose of study treatment
• contact study staff for additional requirements
Exclusion Criteria:
• received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
• received prior androgen deprivation therapy
• pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the first visit through 120 days after the last dose of trial treatment.
• additional cancer that is progressing or has required active treatment within the past 2 years
• contact study staff for additional exclusion criteria
Cancer
Clinics and Surgery Center (CSC), Salivary Gland Carcinoma
Efficacy of Belimumab and Rituximab Compared to Rituximab Alone for the Treatment of Primary Membranous Nephropathy (REBOOT)
People with Primary MN lose more protein in their urine because the filters in their kidneys may be damaged. It is possible that some belimumab may also be lost in the urine because of this. This study will measure belimumab in the blood to decide if people with high urine protein should receive a higher dose of belimumab. Another purpose of this study is to help learn about whether the combination of belimumab and rituximab treatment is effective in making and keeping Primary MN inactive.
Patrick Nachman
18 years and over
STUDY00006831
Inclusion Criteria:
• 18 to 75 years old
• diagnosis of Membranous Nephropathy (MN) or Nephrotic Syndrome (study staff will review specific requirements)
• hypertension while on maximum medications i.e. systolic BP greater than 140mmHg or diastolic greater than 90mmHg
Exclusion Criteria:
• Rituximab use within the previous 12 months
• poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) 9.0% or greater
• women of child-bearing age who are pregnant, nursing, or unwilling to be sexually inactive or use FDA-approved contraception for the duration of the study
• additional medical and mental health exclusions apply, study staff will review
Kidney, Prostate & Urinary
Clinics and Surgery Center (CSC), Membranous Nephropathy, Nephrotic Syndrome
COG ANBL1821 - A Phase 2 Randomized Study of Irinotecan/Temozolomide/Dinutuximab with or without Eflornithine (DFMO) (IND# 141913) in Children with Relapsed, Refractory or Progressive Neuroblastoma
The purpose of this prospective, randomized Phase 2 study is to find out if giving eflornithine (DFMO) along with dinutuximab, irinotecan, and temozolomide is tolerated in patients ≥ 1 year of age. It will also investigate how effective the drug combination is against relapsed or refractory neuroblastoma (NBL).
Emily Greengard
1 year and over
SITE00000576
Inclusion Criteria:
Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e. > 2 x upper limit of normal [ULN]), at the time of initial diagnosis.
For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound as intended to treat high-risk disease. The doses of chemotherapy must be comparable to those used in frontline high-risk neuroblastoma therapies (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, and ANBL1531). Patients must have ONE of the following:
First episode of recurrent high-risk disease following completion of aggressive multi-drug frontline high-risk therapy.
First episode of progressive high-risk disease during aggressive multi-drug frontline therapy.
Primary resistant/refractory disease (less than partial response by International Neuroblastoma Response Criteria [INRC]) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, etc.).
Patients must have at least ONE of the following at the time of enrollment:
Measurable tumor on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable is defined as >= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose F-18 (FDG) uptake on positron emission tomography (PET) scan.
MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction.
Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma. Biopsy is not required for patients who have a new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy.
Patients with bone marrow disease only will be eligible if they have more than 5% disease involvement (documented neuroblastoma cells) in at least one sample from bilateral bone marrow biopsies.
Note: Patients with elevated catecholamines (i.e. > 2 x ULN) only are NOT eligible for this study.
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.
Primary refractory/resistant patients must have received at least 4 cycles of frontline high-risk chemotherapy. Frontline therapy may also have included surgery, chemotherapy, autologous stem cell transplantation (SCT) +/- MIBG, immunotherapy, radiotherapy, and retinoids but must NOT have received second line therapy for resistant/refractory, relapsed, or progressive disease. Patients who received intensified therapy for poor induction response or refractory disease (e.g. MIBG) will be considered to have received second line therapy and will not be eligible.
At least 14 days must have elapsed since completion of myelosuppressive therapy.
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.
No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions. However, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response. Lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma. Palliative radiation while on study is not permitted.
Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell infusions (including stem cell infusions given as supportive care following 131 I-MIBG therapy) as long as hematologic and other eligibility criteria have been met.
Patients are eligible >= 6 weeks after therapeutic 131 I-MIBG provided that all other eligibility criteria are met.
Subjects who have previously received anti-GD2 monoclonal antibodies with or without retinoids for biologic therapy are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy or progressed/relapsed within 3 months of receiving anti-GD2 therapy. However, eligible patients may NOT have received anti-GD2 monoclonal antibodies in combination with chemotherapy.
Subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads are eligible.
Subjects who have previously received DFMO are eligible for this study provided they have not had progressive disease while receiving DFMO or progressed/relapsed within 3 months of completing DFMO.
Patients must not have received long-acting myeloid growth factors (e.g. pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor.
For patients with solid tumors (without marrow involvement) including status post SCT: peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).
For patients with solid tumors (without marrow involvement) including status post SCT: platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and transfusion independent platelet count criteria are met (as above). However, these patients are not evaluable for hematological toxicity.
Creatinine clearance or radioisotope GFR >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
>= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
Total bilirubin =< 1.5 x ULN for age (within 7 days prior to enrollment).
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x ULN for age (=< 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment).
Shortening fraction of >= 27% by echocardiography (ECHO) (within 7 days prior to enrollment).
Ejection fraction of >= 50% by ECHO or gated radionuclide study (within 7 days prior to enrollment).
No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry > 94% if there is a clinical indication for pulse oximetry. Normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung for carbon monoxide [DLCO)] are required if there is a clinical indication for determination. For patients who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT required.
Patients with a history of central nervous system (CNS) disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsants.
CNS toxicity =< grade 2.
Exclusion Criteria:
Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study. Based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study. Because of potential risks to breastfed infants due to drug metabolites that could be excreted in breast milk, female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study. Females of childbearing potential must have a negative pregnancy test to be eligible for this study.
Patients with only elevated catecholamines (i.e. > 2 x ULN) are NOT eligible for this study.
Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment. Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency.
Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not eligible.
Patients must not have received prior treatment with irinotecan and temozolomide.
Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible.
Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible.
Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
Patients with symptoms of congestive heart failure are not eligible.
Patients must not have >= grade 2 diarrhea.
Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not be eligible for this trial. Additionally, patients with significant malabsorption will not be eligible for this trial.
Patients must not have uncontrolled infection.
Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible.MT2019-09: A randomized trial of low versus moderate exposure busulfan for infants with severe combined immunodeficiency (SCID) receiving TCR alpha beta +/CD19+ depleted transplantation: A Phase II study by the Primary Immune Deficiency Treatment Consortium (PIDTC) and Pediatric Blood and Marrow Transplant Consortium (PBMTC) PIDTC CSIDE Protocol (CSIDE)
To determine the incidence of humoral immune reconstitution by 2 years post-transplant in 2 SCID cohorts (IL2RG/JAK3, RAG1/RAG2) undergoing alternative donor HCT by randomized assignment to a busulfan preparative regimen targeted at cumulative area-under-the-curve (cAUC) exposure of 25-35 mg*h/L vs 55-65 mg*h/ L.
Christen Ebens
0 years to 2 years old
SITE00000541
Inclusion Criteria:
• Infants with SCID, either typical or leaky or Omenn syndrome. Typical SCID is defined as either of the following Absence or very low number of T cells (CD3+ T cells <300/microliter AND no or very low T cell function (<10% of lower limit of normal) as measured by response to phytohemagglutinin OR Presence of maternally derived T cells Leaky SCID is defined as the following • Absence of maternally derived T cells • AND either one or both of the following (i, ii): i) <50% of lower limit of normal T cell function as measured by response to PHA OR <30% of lower limit of normal T cell function as measured by response to CD3 ii) Absent or <10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (must document post vaccination or exposure for this criterion to apply) • AND at least two of the following (i through iii): i) CD3 T cells < 1500/microliter ii) >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (at < 4 years of age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower level of normal. Omenn syndrome • Generalized skin rash Maternal lymphocytes tested for and not detected. >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (<2 years of age) Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to antigens (Candida, tetanus) to which the patient has been exposed IF: Proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the patient is eligible as Omenn Syndrome. Hepatomegaly Splenomegaly Lymphadenopathy Elevated IgE Elevated absolute eosinophil count *Oligoclonal T cells measured by CDR3 length or flow cytometry (upload report) *Proliferation to PHA is reduced to < 50% of lower limit of normal (LLN) or SI < 30 *Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells below the lower level of normal
• Documented mutation in one of the following SCID-related genes a. Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1, RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a suitable donor and graft source Haploidentical related mobilized peripheral blood cells 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment Note: to ensure appropriate hepatic metabolism, age at time of busulfan start: For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks
• Adequate organ function defined as: Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥ 26% by echocardiogram. Hepatic: Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and ALT < 5.0 x ULN for age. Renal: GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is < 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be > 50 mL/min/1.73 m2. Pulmonary No need for supplemental oxygen and O2 saturation > 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care).
Exclusion Criteria:
Presence of any serious life-threatening or opportunistic infection at time of enrollment and prior to the initiation of the preparative regimen. Serious infections as defined below that occur after enrollment must be reported immediately to the Study Coordinating Center, and enrollment will be put on hold until the infection resolves. Ideally enrolled subjects will not have had any infection. If patients have experienced infections, these must have resolved by the following definitions:
a. Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site must be negative and patient has completed appropriate course of antibacterial therapy (typically at least 10 days).
ii. Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days).
iii. Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days). If possible, radiographic resolution should also be demonstrated.
b. Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site is negative and patient has completed appropriate course of antifungal therapy (typically at least 14 days). The patient may be continued on antifungal prophylaxis following completion of the treatment course.
c. Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of therapy (typically at least 21 days). If possible, radiographic resolution should also be demonstrated. The patient may be continued on prophylaxis following completion of the treatment course.
d. Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must be re-tested and are negative.
ii. If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible, radiographic resolution should also be demonstrated.
Patients with HIV or HTLV I/II infection will be excluded.GLNE 007 Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas
The purpose of this study if to determine if stool or blood can be used to detect colon cancers as early or earlier than colonoscopy. The researchers plan to use these samples to learn about specific proteins (also known as biomarkers) that may indicate colon polyps, colon cancer or an increased risk of developing colon cancer. In order to learn more about preventing and detecting colon and rectal cancer, we are collecting samples from subjects with cancer, adenomas, and colonoscopies who may be at risk for polyps.
Aasma Shaukat
18 years and over
SITE00001813
Inclusion Criteria:
• at least 18 years old
• able to tolerate giving a blood specimen of up to 60 cc
• willing to collect 1-2 stool samples and prepare a Fecal Immunochemical Test (FIT)
• people who have untreated colon cancer OR have previously removed adenomas, OR have a family history of colon cancer OR have a current positive screening stool test in the past 12 months that hasn't been evaluated
• Healthy Controls: have no history of finding polyps, no family history, or negative colorectal cancer screening test (if performed) within past 12 months
Exclusion Criteria:
• people who have had surgery, radiation, or chemotherapy for their current colorectal cancer or any other cancer
• history or clinically active Inflammatory Bowel Disease
• HIV or chronic active viral hepatitis
• history of cancer in the past 3 years (except minor skin, cervical, or endometrial)
• active chemotherapy or radiation treatment for any purpose
Cancer, Digestive & Liver Health
Colon Cancer, Colon Cancer, Colon Cancer Screening, Colorectal Cancer
COG ACNS1831 - A Phase 3 Randomized Study of Selumetinib (IND # 77782) versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)
Christopher Moertel, MD
2 years to 21 years old
SITE00000735
Inclusion Criteria:
Patients must be >= 2 years and =< 21 years at the time of enrollment
Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or germline genetic testing
Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery
For patients with optic pathway gliomas (OPGs):
Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms (including visual dysfunction, as defined below) or other exam findings associated with the tumor
Previously-diagnosed patients with OPG are eligible if they have new or worsening neurologic symptoms (including visual dysfunction, as defined below) or have tumor growth
For both newly-diagnosed and previously-diagnosed OPG, the patient may be eligible, irrespective of whether there has been tumor growth or other neurological symptoms or worsening, if they meet at least one of the following visual criteria:
Visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year (by examination or history); OR
Significant visual dysfunction (defined as VA worse than normal for age by 0.6 logMAR [20/80, 6/24, or 2.5/10] or more in one or both eyes)
For patients with LGG in other locations (i.e., not OPGs):
Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms or other exam findings associated with the tumor
NOTE: Newly-diagnosed patients with LGG without associated neurologic symptoms or exam findings are not eligible
Previously-diagnosed patients with LGG are eligible if they have new or worsening neurologic symptoms or have tumor growth
Although not required, if a biopsy/tumor resection is performed, eligible histologies will include all tumors considered LGG or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
Patients must have two-dimensional measurable tumor >= 1 cm^2
Patients with metastatic disease or multiple independent primary LGGs are allowed on study
Creatinine clearance or radioisotope glomerular filtration Rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender (within 7 days prior to enrollment) as follows:
Age; maximum serum creatinine (mg/dL)
2 to < 6 years; 0.8 (male) and 0.8 (female)
6 to < 10 years; 1 (male) and 1 (female)
10 to < 13 years; 1.2 (male) and 1.2 (female)
13 to < 16 years; 1.5 (male) and 1.4 (female)
>= 16 years; 1.7 (male) and 1.4 (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
Albumin >= 2 g/dL (within 7 days prior to enrollment)
Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (within 4 weeks prior to enrollment)
Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (within 4 weeks prior to enrollment)
Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to enrollment)
Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
Patients with a known seizure disorder should be stable and should have not experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of enrollment. Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of antihypertensive medications).
Note: Adequate blood pressure can be achieved using medication for the treatment of hypertension
All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
For patients who undergo a surgery on the target tumor (not required), a pre- and post-operative* MRI of the brain (with orbital cuts for optic pathway tumors) or spine (depending on the site(s) of primary disease) with and without contrast must also be performed within 4 weeks prior to enrollment
The post-operative MRIs should be performed ideally within 48 hours after surgery if possible
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 must have the ability to swallow whole capsules
Patients must have receptive and expressive language skills in English or Spanish to complete the quality of life (QOL) and neurocognitive assessments
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 must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
Patients may not be receiving any other investigational agents
Patients with any serious medical or psychiatric illness/ condition, including substance use disorders likely in the judgement of the investigator to interfere or limit compliance with study requirements/treatment are not eligible
Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
Female patients who are pregnant are not eligible 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 are not eligible
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible
Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
Cardiac conditions:
Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
Symptomatic heart failure
New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
Severe valvular heart disease
History of atrial fibrillation
Ophthalmologic conditions:
Current or past history of central serous retinopathy
Current or past history of retinal vein occlusion or retinal detachment
Patients with uncontrolled glaucoma
If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) or longstanding orbito-temporal plexiform neurofibroma (PN), such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Treatments and/or medications patient is receiving that would make her/him ineligible, such as:
Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
Surgery within 2 weeks prior to enrollment, with the exception of surgical placement for vascular access or cerebrospinal fluid (CSF) diverting procedures such as endoscopic third ventriculostomy (ETV) and ventriculo-peritoneal (VP) shunt.
Note: Patients must have healed from any prior surgery prior to enrollment
Patients who have an uncontrolled infection are not eligibleA Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, a AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects with Fabry Disease
Chester Whitley, MD, PhD
18 years and over
STUDY00007094
Inclusion Criteria:
• at least 18 years of age
• diagnosis of Fabry disease
• one or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma
• fully vaccinated for COVID- 19 per CDC guidance
• additional requirements apply for cardiac and renal groups (study staff will review)
Exclusion Criteria:
• history of liver disease
• current or history of use in the last six months of systemic steroids
• other significant medical & mental health diagnosis (study staff will review)
Rare Diseases
Fabry Disease
Extravascular Implantable Cardioverter Defibrillator (EV ICD) Pivotal Study and Continued Access Study (EV ICD)
Henri Roukoz
18 years and over
STUDY00007872
Inclusion Criteria:
• at least 18 years old
• require implantation of an ICD
Exclusion Criteria:
• also need bradycardia pacing or Cardiac Resynchronization Therapy (CRT)
• have an existing pacemaker, ICD, or CRT device implant or leads
• other previous chest surgery or heart diagnosis (study staff will review)
• neurostimulator or any other chronically implanted device that delivers current in the body
• women who are pregnant, breast feeding, or who don't want to use birth control
Heart & Vascular
Clinics and Surgery Center (CSC), EV ICD, Extravascular ICD, Tachycardia, Ventricular Arrhythmia