A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
Study Details
Study Description
Brief Summary
This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, 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. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
PRIMARY OBJECTIVE:
- To compare event-free survival (EFS) in children with de novo acute myeloid leukemia (AML) without FLT3 mutations who are randomly assigned to standard induction therapy on Arm A with daunorubicin, cytarabine (DA) and gemtuzumab ozogamicin (GO) (DA-GO) versus Arm B with CPX-351 and GO.
SECONDARY OBJECTIVES:
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To compare overall survival (OS) and rates of end of Induction 1 (EOI1) minimal residual disease (MRD) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy (Arm A) with DA-GO versus CPX-351 and GO (Arm B).
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To estimate the EFS and rate of EOI1 MRD in FLT3 internal tandem duplication mutation positive patients (FLT3/ITD+; as defined by allelic ratio > 0.1) without favorable cytomolecular characteristics (NPM1 and/or CEBPA) receiving gilteritinib fumarate (gilteritinib) in combination with DA-GO (Arm AC).
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To estimate the EFS and rate of EOI1 MRD in patients with non-ITD FLT3 activating mutations who receive backbone therapy (DA-GO or CPX-351 and GO) with gilteritinib (Arms AD and BD).
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To determine the feasibility of combining gilteritinib and DA-GO or CPX-351 and GO in patients with FLT3/ITD mutations (Arm AC/Arm BC/Arm AD/Arm BD).
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To compare EOI1 MRD and EFS in patients with FLT3/ITD AML+ (allelic ratio [AR] > 0.1) without favorable cytogenetic/molecular characteristics treated with DA-GO-gilteritinib versus (vs) CPX-GO-gilteritinib (Arm AC vs Arm BC).
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To compare the incidence of significant left ventricular systolic dysfunction (LVSD) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy (Arm A) with DA-GO versus CPX-351 and GO (Arm B).
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To compare the changes in echocardiography-derived measures of cardiac function, including left ventricular ejection fraction (EF) and global longitudinal strain (GLS), throughout AML therapy in patients with low and high risk AML without FLT3 mutations receiving Arm A vs Arm B.
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Determine if early changes in sensitive echocardiographic measures of cardiac function (i.e., post-Induction 1 decline in GLS) and elevations in circulating cardiac biomarkers (i.e., cardiac troponin T and N-terminal pro b-type natriuretic peptide) are associated with subsequent declines in left ventricular ejection fraction in patients with non-FLT3 mutant AML receiving therapy on Arms A or B.
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To compare longitudinal acute changes in neuropsychological functioning and neurocognitive late effects between those with central nervous system (CNS) disease and those without CNS disease and between those treated with hematopoietic stem cell transplant (HSCT) and those treated with chemotherapy only for patients on Arms A and B.
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To compare cardiotoxicity measures (EF, GLS, and cardiac biomarkers) in patients receiving standard induction with dexrazoxane hydrochloride (dexrazoxane) vs. CPX-351 in the context of gilteritinib therapy and explore whether the differential cardiotoxicity across arms varies from that observed in non-FLT3 mutant AML without gilteritinib exposure.
EXPLORATORY OBJECTIVES:
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To estimate the EFS and rate of EOI1 MRD in patients with high allelic ratio (HAR) FLT3/ITD+ patients, as historically defined by an AR > 0.4, receiving gilteritinib in combination with DA-GO (Arm AC with AR > 0.4).
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To estimate the EFS, OS, and rate of EOI1 MRD in FLT3/ITD+ patients (as defined by allelic ratio > 0.1) with NPM1 and/or bZIP CEBPA mutations receiving gilteritinib in combination with DA-GO (Arm AC).
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Compare the changes in high sensitivity troponin and natriuretic peptide elevations throughout AML therapy, as measured at the end of each chemotherapy course, in patients with low and high risk AML without FLT3 mutations receiving Arm A vs Arm B.
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Quantify the association of host factors (age, sex, body mass index [BMI], race), treatment exposures (cumulative anthracycline dose, anthracycline arm, hematopoietic stem cell transplant vs. chemotherapy alone), early declines in GLS, and elevations in cardiac biomarkers (cTnT and NT-proBNP) with subsequent LVSD.
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To describe the rates of CNS disease utilizing an updated strategy for diagnosing and defining CNS disease in pediatric AML.
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To describe the rates of CNS relapse (both isolated CNS and combined bone marrow/CNS) when utilizing this updated strategy as well as changing CNS prophylaxis and treatment to include triple intrathecal chemotherapy.
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To describe the rate of bone marrow measurable residual disease, detected by multi-dimensional flow cytometry, prior to hematopoietic stem cell transplant (HSCT).
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To describe plasma metabolomics that may impact efficacy, toxicity, and/or pharmacokinetics of allogeneic HSCT.
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To estimate the prevalence of non-risk stratifying cytogenetic/molecular variants and assess their impact on outcome in childhood AML.
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To describe the pharmacokinetic parameters of plasma cytarabine and daunorubicin after CPX-351 administration to pediatric and young adult patients with new diagnosis of AML.
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To describe the pharmacokinetic parameters of orally administered gilteritinib when administered to pediatric and young adult patients with new diagnosis of AML.
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To describe the pharmacodynamic parameters of gilteritinib using the FLT3 plasma inhibitory activity assay (PIA) when administered to children and young adults with new diagnosis of AML and FLT3 mutations.
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To estimate OS in patients with FLT3/ITD+ AML (AR > 0.1) without favorable cytogenetic/molecular characteristics treated with DA-GO-gilteritinib or CPX-351-GO-gilteritinib (Separate analyses will be conducted for Arm AC vs Arm BC).
OUTLINE: Patients are randomized to either Arm A or B and assigned to Arm C or D based on FLT3 testing results.
Risk group assignments are calculated based on cytogenetic, molecular and genomic findings (details in protocol)
Risk groups include (Details in protocol):
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Low Risk 1 (LR1)
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Low Risk 2 (LR2)
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High Risk (HR)
TREATMENT FOR PATIENTS WITHOUT FLT3 MUTATIONS:
ARM A LOW RISK GROUP 1:
INDUCTION 1: Patients receive cytarabine intravenously (IV) over 1-30 minutes every 12 hours (Q12H) on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate intrathecally (IT), therapeutic hydrocortisone (hydrocortisone) IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT once weekly (QW) starting on day 8 for 4-6 weeks (may continue into Induction 2) until the cerebral spinal fluid (CSF) is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5.
INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.
INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi intramuscularly (IM) or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.
ARM B LOW RISK GROUP 1:
INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5.
INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.
INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.
ARM A LOW RISK GROUP 2:
INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5.
INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.
INTENSIFICATION 2: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4 and dexrazoxane IV over 5-15 minutes and mitoxantrone hydrochloride (mitoxantrone) IV over 5-15 minutes on days 3-6.
INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.
ARM B LOW RISK GROUP 2:
INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5.
INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.
INTENSIFICATION 2: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4 and dexrazoxane IV over 5-15 minutes and mitoxantrone hydrochloride (mitoxantrone) IV over 5-15 minutes on days 3-6.
INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.
ARM A HIGH RISK GROUP:
INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5.
INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.
HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.
ARM B HIGH RISK GROUP:
INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5.
INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.
HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.
TREATMENT FOR PATIENTS WITH FLT3/ITD MUTATIONS (ITD AR > 0.1):
ARM AC LOW RISK GROUP 2:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.
INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via nasogastric (NG) or gastronomy (G) tube daily on days 1-365.
ARM BC LOW RISK GROUP 2:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.
INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
ARM AC HIGH RISK GROUP:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.
POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
ARM BC HIGH RISK GROUP:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.
POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
TREATMENT FOR NON-ITD FLT3 ACTIVATING MUTATIONS:
ARM AD LOW RISK GROUP 2:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.
INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
ARM BD LOW RISK GROUP 2:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.
INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
ARM AD HIGH RISK GROUP:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.
POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
ARM BD HIGH RISK GROUP:
CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).
INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.
INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.
HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.
POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.
NOTE: During Induction 2 or Intensification 2, patients in Arms A and B with left ventricular systolic dysfunction receive a replacement course of high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9, and asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. Patients in Arms AC, BC, AD, and BD receive treatment as in Arms A and B and also receive gilteritinib PO QD on days 10-37 (Induction 2) or days 10-37 (Intensification 2).
All treatment continues in the absence of disease progression or unacceptable toxicity.
OPTIONAL NEUROCOGNITIVE STUDY:
Patients may complete the Cogstate assessment battery at the end of Induction 1, at the end of therapy, and at 9 and 60 months post-enrollment.
After completion of study treatment, patients are followed up monthly for 6 months and then every other mon
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A High Risk Group Arm A High Risk Group: See Detailed Description. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm A Low Risk Group 1 Arm A Low Risk Group 1: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm A Low Risk Group 2 Arm A Low Risk Group 2: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm AC High Risk Group Arm AC High Risk Group: See Detailed Description. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm AC Low Risk Group 2 Arm AC Low Risk Group 2: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm AD High Risk Group Arm AD High Risk Group: See Detailed Description. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm AD Low Risk Group 2 Arm AD Low Risk Group 2: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm B High Risk Group Arm B High Risk Group: See Detailed Description. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm B Low Risk Group 1 Arm B Low Risk Group 1: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm B Low Risk Group 2 Arm B Low Risk Group 2: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm BC High Risk Group Arm BC High Risk Group: See Detailed Description. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm BC Low Risk Group 2 Arm BC Low Risk Group 2: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm BD High Risk Group Arm BD High Risk Group: See Detailed Description. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Experimental: Arm BD Low Risk Group 2 Arm BD Low Risk Group 2: See Detailed Description. |
Drug: Asparaginase
Given IM or IV
Other Names:
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Other Names:
Behavioral: Cogstate Assessment Battery
Ancillary studies
Drug: Cytarabine
Given IV or IT
Other Names:
Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
Drug: Gilteritinib Fumarate
Given PO or via NG or G tube
Other Names:
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
Drug: Methotrexate
Given IT
Other Names:
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Event-free survival (EFS) [Up to 3 years]
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
Secondary Outcome Measures
- Overall survival (OS) [Up to 3 years]
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
- Proportion of patients positive for minimal residual disease (MRD+) [Up to 4 weeks]
The proportion of patients MRD+ at end of induction 1 (EOI1) will be estimated as the number of patients MRD+ divided by the number of patients with evaluable EOI1 MRD results along with a corresponding 95% confidence interval determined using a binomial exact method.
- Proportion of patients who died during protocol therapy [Up to 2 years]
The proportion of patients who died during protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method.
- Relapse rate [Up to 3 years]
Cumulative incidence estimates will be used to determine the 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events.
- Treatment-related mortality rate (TRM) [Up to 3 years]
Cumulative incidence estimates will be used to determine the 3 year TRM defined as time from study entry to death where induction failure, relapse or secondary malignancies are competing events.
- Incidence of adverse events [Up to 2 years]
The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Other Outcome Measures
- Course duration [Up to 2 years]
Median and range of the length of course duration will be determined.
- Length of hospitalization [Up to 2 years]
Median and range of the length of hospitalization time during protocol therapy will be determined.
- Time to count recovery [Up to 2 years]
Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery in days where deaths are competing events.
Eligibility Criteria
Criteria
Inclusion Criteria:
- All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part
- prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures
-
Patients must be less than 22 years of age at the time of study enrollment
-
Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
-
Patient must have 1 of the following:
-
= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
-
In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
-
< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
-
A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
-
ARM C: Patient must be >= 2 years of age at the time of Late Callback
-
ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology
-
ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
-
ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
-
ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
-
ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
-
ARM D: Patient must be >= 2 years of age at the time of Late Callback
-
ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
-
ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
-
ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
-
ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
-
NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
-
NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
-
NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
-
NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
-
NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
-
All patients and/or their parents or legal guardians must sign a written informed consent
-
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
-
Fanconi anemia
-
Shwachman Diamond syndrome
-
Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
-
Telomere disorders
-
Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
-
Any concurrent malignancy
-
Juvenile myelomonocytic leukemia (JMML)
-
Philadelphia chromosome positive AML
-
Mixed phenotype acute leukemia
-
Acute promyelocytic leukemia
-
Acute myeloid leukemia arising from myelodysplasia
-
Therapy-related myeloid neoplasms
-
Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) < 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
-
Administration of prior anti-cancer therapy except as outlined below:
-
Hydroxyurea
-
All-trans retinoic acid (ATRA)
-
Corticosteroids (any route)
-
Intrathecal therapy given at diagnosis
-
In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
-
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
-
Lactating females who plan to breastfeed their infants
-
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
-
ARM D: Patient does not have any congenital long QT syndrome or congenital heart block
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
2 | USA Health Strada Patient Care Center | Mobile | Alabama | United States | 36604 |
3 | Banner Children's at Desert | Mesa | Arizona | United States | 85202 |
4 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
5 | Banner University Medical Center - Tucson | Tucson | Arizona | United States | 85719 |
6 | Arkansas Children's Hospital | Little Rock | Arkansas | United States | 72202-3591 |
7 | Kaiser Permanente Downey Medical Center | Downey | California | United States | 90242 |
8 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
9 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
10 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
11 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
12 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
13 | Mattel Children's Hospital UCLA | Los Angeles | California | United States | 90095 |
14 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
15 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
16 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
17 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
18 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
19 | UCSF Medical Center-Mission Bay | San Francisco | California | United States | 94158 |
20 | Santa Barbara Cottage Hospital | Santa Barbara | California | United States | 93102 |
21 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
22 | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado | United States | 80218 |
23 | Connecticut Children's Medical Center | Hartford | Connecticut | United States | 06106 |
24 | Yale University | New Haven | Connecticut | United States | 06520 |
25 | Alfred I duPont Hospital for Children | Wilmington | Delaware | United States | 19803 |
26 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
27 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
28 | Broward Health Medical Center | Fort Lauderdale | Florida | United States | 33316 |
29 | Golisano Children's Hospital of Southwest Florida | Fort Myers | Florida | United States | 33908 |
30 | University of Florida Health Science Center - Gainesville | Gainesville | Florida | United States | 32610 |
31 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
32 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
33 | Palms West Radiation Therapy | Loxahatchee Groves | Florida | United States | 33470 |
34 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
35 | Nicklaus Children's Hospital | Miami | Florida | United States | 33155 |
36 | AdventHealth Orlando | Orlando | Florida | United States | 32803 |
37 | Arnold Palmer Hospital for Children | Orlando | Florida | United States | 32806 |
38 | Nemours Children's Hospital | Orlando | Florida | United States | 32827 |
39 | Sacred Heart Hospital | Pensacola | Florida | United States | 32504 |
40 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
41 | Tampa General Hospital | Tampa | Florida | United States | 33606 |
42 | Saint Joseph's Hospital/Children's Hospital-Tampa | Tampa | Florida | United States | 33607 |
43 | Saint Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
44 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
45 | Augusta University Medical Center | Augusta | Georgia | United States | 30912 |
46 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31404 |
47 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
48 | Saint Luke's Cancer Institute - Boise | Boise | Idaho | United States | 83712 |
49 | Lurie Children's Hospital-Chicago | Chicago | Illinois | United States | 60611 |
50 | University of Illinois | Chicago | Illinois | United States | 60612 |
51 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
52 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
53 | Advocate Children's Hospital-Park Ridge | Park Ridge | Illinois | United States | 60068 |
54 | Saint Jude Midwest Affiliate | Peoria | Illinois | United States | 61637 |
55 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
56 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
57 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
58 | Blank Children's Hospital | Des Moines | Iowa | United States | 50309 |
59 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
60 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
61 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
62 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
63 | Ochsner Medical Center Jefferson | New Orleans | Louisiana | United States | 70121 |
64 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
65 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
66 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
67 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
68 | Walter Reed National Military Medical Center | Bethesda | Maryland | United States | 20889-5600 |
69 | Tufts Children's Hospital | Boston | Massachusetts | United States | 02111 |
70 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
71 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
72 | UMass Memorial Medical Center - University Campus | Worcester | Massachusetts | United States | 01655 |
73 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
74 | Ascension Saint John Hospital | Detroit | Michigan | United States | 48236 |
75 | Michigan State University Clinical Center | East Lansing | Michigan | United States | 48824-7016 |
76 | Helen DeVos Children's Hospital at Spectrum Health | Grand Rapids | Michigan | United States | 49503 |
77 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
78 | Beaumont Children's Hospital-Royal Oak | Royal Oak | Michigan | United States | 48073 |
79 | Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis | Minnesota | United States | 55404 |
80 | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota | United States | 55455 |
81 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
82 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
83 | Columbia Regional | Columbia | Missouri | United States | 65201 |
84 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
85 | Cardinal Glennon Children's Medical Center | Saint Louis | Missouri | United States | 63104 |
86 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
87 | Mercy Hospital Saint Louis | Saint Louis | Missouri | United States | 63141 |
88 | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska | United States | 68114 |
89 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
90 | University Medical Center of Southern Nevada | Las Vegas | Nevada | United States | 89102 |
91 | Sunrise Hospital and Medical Center | Las Vegas | Nevada | United States | 89109 |
92 | Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Las Vegas | Nevada | United States | 89135 |
93 | Summerlin Hospital Medical Center | Las Vegas | Nevada | United States | 89144 |
94 | Renown Regional Medical Center | Reno | Nevada | United States | 89502 |
95 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
96 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
97 | Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
98 | Saint Peter's University Hospital | New Brunswick | New Jersey | United States | 08901 |
99 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
100 | Newark Beth Israel Medical Center | Newark | New Jersey | United States | 07112 |
101 | Saint Joseph's Regional Medical Center | Paterson | New Jersey | United States | 07503 |
102 | Albany Medical Center | Albany | New York | United States | 12208 |
103 | Montefiore Medical Center - Moses Campus | Bronx | New York | United States | 10467 |
104 | Maimonides Medical Center | Brooklyn | New York | United States | 11219 |
105 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
106 | NYU Winthrop Hospital | Mineola | New York | United States | 11501 |
107 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
108 | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York | United States | 10016 |
109 | Mount Sinai Hospital | New York | New York | United States | 10029 |
110 | NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York | United States | 10032 |
111 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
112 | NYP/Weill Cornell Medical Center | New York | New York | United States | 10065 |
113 | University of Rochester | Rochester | New York | United States | 14642 |
114 | Stony Brook University Medical Center | Stony Brook | New York | United States | 11794 |
115 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
116 | New York Medical College | Valhalla | New York | United States | 10595 |
117 | Mission Hospital | Asheville | North Carolina | United States | 28801 |
118 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
119 | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina | United States | 28203 |
120 | Novant Health Presbyterian Medical Center | Charlotte | North Carolina | United States | 28204 |
121 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
122 | East Carolina University | Greenville | North Carolina | United States | 27834 |
123 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
124 | Sanford Broadway Medical Center | Fargo | North Dakota | United States | 58122 |
125 | Children's Hospital Medical Center of Akron | Akron | Ohio | United States | 44308 |
126 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
127 | Rainbow Babies and Childrens Hospital | Cleveland | Ohio | United States | 44106 |
128 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
129 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
130 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
131 | ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Toledo | Ohio | United States | 43606 |
132 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
133 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
134 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
135 | Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | United States | 18103 |
136 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
137 | Penn State Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
138 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
139 | Saint Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
140 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
141 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
142 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
143 | Prisma Health Richland Hospital | Columbia | South Carolina | United States | 29203 |
144 | BI-LO Charities Children's Cancer Center | Greenville | South Carolina | United States | 29605 |
145 | Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | United States | 57117-5134 |
146 | T C Thompson Children's Hospital | Chattanooga | Tennessee | United States | 37403 |
147 | East Tennessee Childrens Hospital | Knoxville | Tennessee | United States | 37916 |
148 | The Children's Hospital at TriStar Centennial | Nashville | Tennessee | United States | 37203 |
149 | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
150 | Dell Children's Medical Center of Central Texas | Austin | Texas | United States | 78723 |
151 | Driscoll Children's Hospital | Corpus Christi | Texas | United States | 78411 |
152 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
153 | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas | United States | 75390 |
154 | El Paso Children's Hospital | El Paso | Texas | United States | 79905 |
155 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
156 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
157 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
158 | Children's Hospital of San Antonio | San Antonio | Texas | United States | 78207 |
159 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
160 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
161 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
162 | Primary Children's Hospital | Salt Lake City | Utah | United States | 84113 |
163 | University of Vermont and State Agricultural College | Burlington | Vermont | United States | 05405 |
164 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
165 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
166 | Naval Medical Center - Portsmouth | Portsmouth | Virginia | United States | 23708-2197 |
167 | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | United States | 23298 |
168 | Carilion Children's | Roanoke | Virginia | United States | 24014 |
169 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
170 | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington | United States | 99204 |
171 | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington | United States | 98405 |
172 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431 |
173 | West Virginia University Charleston Division | Charleston | West Virginia | United States | 25304 |
174 | Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | United States | 54301 |
175 | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | United States | 53792 |
176 | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin | United States | 54449 |
177 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
178 | University of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
179 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
180 | IWK Health Centre | Halifax | Nova Scotia | Canada | B3K 6R8 |
181 | McMaster Children's Hospital at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8N 3Z5 |
182 | Children's Hospital | London | Ontario | Canada | N6A 5W9 |
183 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
184 | Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
185 | The Montreal Children's Hospital of the MUHC | Montreal | Quebec | Canada | H3H 1P3 |
186 | Centre Hospitalier Universitaire Sainte-Justine | Montreal | Quebec | Canada | H3T 1C5 |
187 | Centre Hospitalier Universitaire de Quebec | Quebec | Canada | G1V 4G2 | |
188 | University Pediatric Hospital | San Juan | Puerto Rico | 00926 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Todd M Cooper, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AAML1831
- NCI-2020-00546
- AAML1831
- AAML1831
- U10CA180886