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
NCT ID: NCT04293562
Last Updated: 2025-12-22
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE3
Total Enrollment
1186 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-07-21
Study Completion Date
2029-06-30
Brief Summary
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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.
Detailed Description
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PRIMARY OBJECTIVE:
I. 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:
I. 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).
II. 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).
III. 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).
IV. To determine the feasibility of combining gilteritinib and DA-GO or CPX-351 and GO in patients with FLT3/ITD and FLT3/TKD mutations (Arm AC/Arm BC/Arm AD/Arm BD).
V. 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).
VI. 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).
VII. 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.
VIII. 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.
IX. 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.
X. 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:
I. 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).
II. 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).
III. 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.
IV. 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.
V. To describe the rates of CNS disease utilizing an updated strategy for diagnosing and defining CNS disease in pediatric AML.
VI. 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.
VII. To describe the rate of bone marrow measurable residual disease, detected by multi-dimensional flow cytometry, prior to hematopoietic stem cell transplant (HSCT).
VIII. To describe plasma metabolomics that may impact efficacy, toxicity, and/or pharmacokinetics of allogeneic HSCT.
IX. To estimate the prevalence of non-risk stratifying cytogenetic/molecular variants and assess their impact on outcome in childhood AML.
X. 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.
XI. To describe the pharmacokinetic parameters of orally administered gilteritinib when administered to pediatric and young adult patients with new diagnosis of AML.
XII. 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.
XIII. 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. As of 11/19/24 arms B, BC and BD are closed and new patients receive treatment in Arm A Low Risk Group 2 Induction 1 or Arm A High Risk Induction 1, and then assigned to arm AC or AD per FLT3 results.
Risk group assignments are calculated based on cytogenetic, molecular and genomic findings (details in protocol)
1. Low Risk 1
2. Low Risk 2
3. High Risk
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 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 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) on days 2 and 9 or IV over 1-2 hours 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 on days 2 and 9 or IV over 1-2 hours 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 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 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 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 on days 2 and 9 or IV over 1-2 hours 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 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 on days 2 and 9 or IV over 1-2 hours 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 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 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 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)/nasogastric (NG)/gastrostomy (G)-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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/NG/G-tube 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/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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 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 PO/NG/G-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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/NG/G-tube QD 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/NG/G-tube 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/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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/NG/G-tube QD 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 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 PO/NG/G-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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/NG/G-tube 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/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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 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 PO/NG/G-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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 6-26.
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 or NG or G tube QD 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 11-31.
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 6-26.
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 or NG or G tube QD 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. Patients in Arms AC, BC, AD, and BD receive treatment as in Arms A and B and also receive gilteritinib PO QD on days 10-30 (Induction 2) or days 10-30 (Intensification 2).
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.
I. 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:
I. 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).
II. 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).
III. 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).
IV. To determine the feasibility of combining gilteritinib and DA-GO or CPX-351 and GO in patients with FLT3/ITD and FLT3/TKD mutations (Arm AC/Arm BC/Arm AD/Arm BD).
V. 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).
VI. 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).
VII. 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.
VIII. 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.
IX. 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.
X. 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:
I. 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).
II. 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).
III. 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.
IV. 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.
V. To describe the rates of CNS disease utilizing an updated strategy for diagnosing and defining CNS disease in pediatric AML.
VI. 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.
VII. To describe the rate of bone marrow measurable residual disease, detected by multi-dimensional flow cytometry, prior to hematopoietic stem cell transplant (HSCT).
VIII. To describe plasma metabolomics that may impact efficacy, toxicity, and/or pharmacokinetics of allogeneic HSCT.
IX. To estimate the prevalence of non-risk stratifying cytogenetic/molecular variants and assess their impact on outcome in childhood AML.
X. 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.
XI. To describe the pharmacokinetic parameters of orally administered gilteritinib when administered to pediatric and young adult patients with new diagnosis of AML.
XII. 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.
XIII. 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. As of 11/19/24 arms B, BC and BD are closed and new patients receive treatment in Arm A Low Risk Group 2 Induction 1 or Arm A High Risk Induction 1, and then assigned to arm AC or AD per FLT3 results.
Risk group assignments are calculated based on cytogenetic, molecular and genomic findings (details in protocol)
1. Low Risk 1
2. Low Risk 2
3. High Risk
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 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 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) on days 2 and 9 or IV over 1-2 hours 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 on days 2 and 9 or IV over 1-2 hours 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 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 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 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 on days 2 and 9 or IV over 1-2 hours 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 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 on days 2 and 9 or IV over 1-2 hours 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 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 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 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)/nasogastric (NG)/gastrostomy (G)-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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/NG/G-tube 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/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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 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 PO/NG/G-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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/NG/G-tube QD 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/NG/G-tube 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/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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/NG/G-tube QD 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 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 PO/NG/G-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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/NG/G-tube 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/NG/G-tube QD on days 11-31.
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/NG/G-tube QD on days 6-26.
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 15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO/NG/G-tube QD on days 7-27.
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 gilteritinib PO/NG/G-tube QD on days 10-30.
POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO/NG/G-tube QD 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 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 PO/NG/G-tube 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 15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO/NG/G-tube QD on days 11-31.
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 6-26.
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 or NG or G tube QD 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 11-31.
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 6-26.
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 or NG or G tube QD 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. Patients in Arms AC, BC, AD, and BD receive treatment as in Arms A and B and also receive gilteritinib PO QD on days 10-30 (Induction 2) or days 10-30 (Intensification 2).
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.
Conditions
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Acute Myeloid Leukemia
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
Group Type
EXPERIMENTAL
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
PROCEDURE
Undergo allogeneic HSCT
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Mitoxantrone Hydrochloride
Intervention Type
DRUG
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
Group Type
EXPERIMENTAL
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
PROCEDURE
Undergo allogeneic HSCT
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Mitoxantrone Hydrochloride
Intervention Type
DRUG
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
Group Type
EXPERIMENTAL
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
PROCEDURE
Undergo allogeneic HSCT
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Daunorubicin Hydrochloride
Intervention Type
DRUG
Given IV
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Mitoxantrone Hydrochloride
Intervention Type
DRUG
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
PROCEDURE
Undergo allogeneic HSCT
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Methotrexate
Intervention Type
DRUG
Given IT
Mitoxantrone Hydrochloride
Intervention Type
DRUG
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
PROCEDURE
Undergo allogeneic HSCT
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Mitoxantrone Hydrochloride
Intervention Type
DRUG
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Allogeneic Hematopoietic Stem Cell Transplantation
Intervention Type
PROCEDURE
Undergo allogeneic HSCT
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Group Type
EXPERIMENTAL
Asparaginase Erwinia chrysanthemi
Intervention Type
DRUG
Given IM or IV
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Bone Marrow Aspiration
Intervention Type
PROCEDURE
Undergo BM aspiration
Bone Marrow Biopsy
Intervention Type
PROCEDURE
BM biopsy
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Cytarabine
Intervention Type
DRUG
Given IV or IT
Dexrazoxane Hydrochloride
Intervention Type
DRUG
Given IV
Etoposide
Intervention Type
DRUG
Given IV
Fludeoxyglucose F-18
Intervention Type
OTHER
Undergo FDG-PET
Gemtuzumab Ozogamicin
Intervention Type
DRUG
Given IV
Gilteritinib Fumarate
Intervention Type
DRUG
Given PO/NG/G-tube
Liposome-encapsulated Daunorubicin-Cytarabine
Intervention Type
DRUG
Given IV
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Methotrexate
Intervention Type
DRUG
Given IT
Mitoxantrone Hydrochloride
Intervention Type
DRUG
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo FDG-PET
Questionnaire Administration
Intervention Type
OTHER
Ancillary studies
Therapeutic Hydrocortisone
Intervention Type
DRUG
Given IT
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Intervention Type
PROCEDURE
Asparaginase Erwinia chrysanthemi
Given IM or IV
Intervention Type
DRUG
Biospecimen Collection
Undergo blood sample collection
Intervention Type
PROCEDURE
Bone Marrow Aspiration
Undergo BM aspiration
Intervention Type
PROCEDURE
Bone Marrow Biopsy
BM biopsy
Intervention Type
PROCEDURE
Computed Tomography
Undergo CT
Intervention Type
PROCEDURE
Cytarabine
Given IV or IT
Intervention Type
DRUG
Daunorubicin Hydrochloride
Given IV
Intervention Type
DRUG
Dexrazoxane Hydrochloride
Given IV
Intervention Type
DRUG
Etoposide
Given IV
Intervention Type
DRUG
Fludeoxyglucose F-18
Undergo FDG-PET
Intervention Type
OTHER
Gemtuzumab Ozogamicin
Given IV
Intervention Type
DRUG
Gilteritinib Fumarate
Given PO/NG/G-tube
Intervention Type
DRUG
Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Intervention Type
DRUG
Magnetic Resonance Imaging
Undergo MRI
Intervention Type
PROCEDURE
Methotrexate
Given IT
Intervention Type
DRUG
Mitoxantrone Hydrochloride
Given IV
Intervention Type
DRUG
Positron Emission Tomography
Undergo FDG-PET
Intervention Type
PROCEDURE
Questionnaire Administration
Ancillary studies
Intervention Type
OTHER
Therapeutic Hydrocortisone
Given IT
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Allogeneic
Allogeneic Hematopoietic Cell Transplantation
Allogeneic Stem Cell Transplantation
HSC
HSCT
Stem Cell Transplantation, Allogeneic
Asparaginase Erwinia chrysanthemi (Recombinant)-rywn
Asparaginase Erwinia chrysanthemi, Recombinant-rywn
Asparaginase Erwinia chrysanthemi-rywn
Crisantaspase
Crisantaspase Biobetter JZP-458
Crisantaspasum
Enrylaze
Erwinase
Erwinaze
JZP 458
JZP-458
JZP458
PF743
RC-P JZP-458
Recombinant Asparaginase erwinia chrysanthemi JZP-458
Recombinant Crisantaspase JZP-458
Recombinant Erwinia asparaginase JZP-458
Rylaze
Biological Sample Collection
Biospecimen Collected
Specimen Collection
Biopsy of Bone Marrow
Biopsy, Bone Marrow
CAT
CAT Scan
Computed Axial Tomography
Computerized Axial Tomography
Computerized axial tomography (procedure)
Computerized Tomography
Computerized Tomography (CT) scan
CT
CT Scan
Diagnostic CAT Scan
Diagnostic CAT Scan Service Type
tomography
.beta.-Cytosine arabinoside
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-.beta.-D-Arabinofuranosylcytosine
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-Beta-D-arabinofuranosylcytosine
1.beta.-D-Arabinofuranosylcytosine
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Alexan
Ara-C
ARA-cell
Arabine
Arabinofuranosylcytosine
Arabinosylcytosine
Aracytidine
Aracytin
Aracytine
Beta-Cytosine Arabinoside
CHX-3311
Cytarabinum
Cytarbel
Cytosar
Cytosine Arabinoside
Cytosine-.beta.-arabinoside
Cytosine-beta-arabinoside
Erpalfa
Starasid
Tarabine PFS
U 19920
U-19920
Udicil
WR-28453
Cerubidin
Cerubidine
Cloridrato de Daunorubicina
Daunoblastin
Daunoblastina
Daunoblastine
Daunomycin Hydrochloride
Daunomycin, hydrochloride
Daunorubicin.HCl
Daunorubicini Hydrochloridum
FI-6339
Ondena
RP-13057
Rubidomycin Hydrochloride
Rubilem
Cardioxane
Totect
Zinecard
Demethyl Epipodophyllotoxin Ethylidine Glucoside
EPEG
Lastet
Toposar
Vepesid
VP 16
VP 16-213
VP 16213
VP-16
VP-16-213
VP-16213
VP16
VP16213
18FDG
FDG
Fludeoxyglucose (18F)
fludeoxyglucose F 18
Fludeoxyglucose F18
Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
Fluorodeoxyglucose F18
Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
CDP-771
CMA-676
gemtuzumab
hP67.6-Calicheamicin
Mylotarg
WAY-CMA-676
ASP-2215 Hemifumarate
ASP2215 Hemifumarate
Gilteritinib Hemifumarate
Xospata
CPX 351
CPX-351
CPX351
Cytarabine and Daunorubicin Liposomal
Cytarabine-Daunorubicin Liposome for Injection
Daunorubicin and Cytarabine (Liposomal)
Liposomal AraC-Daunorubicin CPX-351
Liposomal Cytarabine-Daunorubicin
Liposome-encapsulated Combination of Daunorubicin and Cytarabine
Vyxeos
Magnetic Resonance
Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging (procedure)
Magnetic Resonance Imaging Scan
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
MR
MR Imaging
MRI
MRI Scan
MRIs
NMR Imaging
NMRI
Nuclear Magnetic Resonance Imaging
sMRI
Structural MRI
Abitrexate
Alpha-Methopterin
Amethopterin
Brimexate
CL 14377
CL-14377
Emtexate
Emthexat
Emthexate
Farmitrexat
Fauldexato
Folex
Folex PFS
Jylamvo
Lantarel
Ledertrexate
Lumexon
Maxtrex
Medsatrexate
Metex
Methoblastin
Methotrexate LPF
Methotrexate Methylaminopterin
Methotrexatum
Metotrexato
Metrotex
Mexate
Mexate-AQ
MTX
Novatrex
Rheumatrex
Texate
Tremetex
Trexeron
Trixilem
WR-19039
CL 232315
DHAD
DHAQ
Dihydroxyanthracenedione Dihydrochloride
Mitoxantrone Dihydrochloride
Mitoxantroni Hydrochloridum
Mitozantrone Hydrochloride
Mitroxone
Neotalem
Novantrone
Onkotrone
Pralifan
Medical Imaging, Positron Emission Tomography
PET
PET Scan
Positron emission tomography (procedure)
Positron Emission Tomography Scan
Positron-Emission Tomography
PT
Aeroseb-HC
Barseb HC
Barseb-HC
Cetacort
Cort-Dome
Cortef
Cortenema
Cortifan
Cortisol
Cortispray
Cortril
Dermacort
Domolene
Eldecort
Hautosone
Heb-Cort
Hydrocortisone
Hydrocortone
Hytone
Komed-HC
Nutracort
Proctocort
Rectoid
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831
* 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
* 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
* 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
Maximum Eligible Age
21 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Cancer Institute (NCI)
NIH
Sponsor Role
collaborator
Children's Oncology Group
NETWORK
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Todd M Cooper
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital of Alabama
Birmingham, Alabama, United States
Site Status
RECRUITING
USA Health Strada Patient Care Center
Mobile, Alabama, United States
Site Status
RECRUITING
Banner Children's at Desert
Mesa, Arizona, United States
Site Status
RECRUITING
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Site Status
RECRUITING
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Site Status
RECRUITING
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Site Status
RECRUITING
Kaiser Permanente Downey Medical Center
Downey, California, United States
Site Status
RECRUITING
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Site Status
RECRUITING
Loma Linda University Medical Center
Loma Linda, California, United States
Site Status
RECRUITING
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Site Status
RECRUITING
Children's Hospital Los Angeles
Los Angeles, California, United States
Site Status
RECRUITING
Cedars Sinai Medical Center
Los Angeles, California, United States
Site Status
RECRUITING
Mattel Children's Hospital UCLA
Los Angeles, California, United States
Site Status
RECRUITING
Valley Children's Hospital
Madera, California, United States
Site Status
RECRUITING
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Site Status
RECRUITING
Kaiser Permanente-Oakland
Oakland, California, United States
Site Status
RECRUITING
Children's Hospital of Orange County
Orange, California, United States
Site Status
RECRUITING
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Site Status
RECRUITING
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Site Status
RECRUITING
Rady Children's Hospital - San Diego
San Diego, California, United States
Site Status
RECRUITING
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Site Status
RECRUITING
Santa Barbara Cottage Hospital
Santa Barbara, California, United States
Site Status
RECRUITING
Children's Hospital Colorado
Aurora, Colorado, United States
Site Status
RECRUITING
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, United States
Site Status
RECRUITING
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Site Status
RECRUITING
Yale University
New Haven, Connecticut, United States
Site Status
RECRUITING
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Site Status
RECRUITING
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Site Status
RECRUITING
Children's National Medical Center
Washington D.C., District of Columbia, United States
Site Status
RECRUITING
Broward Health Medical Center
Fort Lauderdale, Florida, United States
Site Status
ACTIVE_NOT_RECRUITING
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
Site Status
RECRUITING
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States
Site Status
RECRUITING
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
Site Status
RECRUITING
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
Site Status
RECRUITING
Palms West Radiation Therapy
Loxahatchee Groves, Florida, United States
Site Status
ACTIVE_NOT_RECRUITING
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Site Status
RECRUITING
Nicklaus Children's Hospital
Miami, Florida, United States
Site Status
RECRUITING
AdventHealth Orlando
Orlando, Florida, United States
Site Status
RECRUITING
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Site Status
RECRUITING
Nemours Children's Hospital
Orlando, Florida, United States
Site Status
RECRUITING
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
Site Status
RECRUITING
Sacred Heart Hospital
Pensacola, Florida, United States
Site Status
ACTIVE_NOT_RECRUITING
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Site Status
RECRUITING
Tampa General Hospital
Tampa, Florida, United States
Site Status
RECRUITING
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Site Status
RECRUITING
Saint Mary's Medical Center
West Palm Beach, Florida, United States
Site Status
RECRUITING
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Site Status
RECRUITING
Augusta University Medical Center
Augusta, Georgia, United States
Site Status
RECRUITING
Memorial Health University Medical Center
Savannah, Georgia, United States
Site Status
RECRUITING
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Site Status
RECRUITING
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Site Status
RECRUITING
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Site Status
RECRUITING
University of Illinois
Chicago, Illinois, United States
Site Status
RECRUITING
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Site Status
RECRUITING
Loyola University Medical Center
Maywood, Illinois, United States
Site Status
RECRUITING
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, United States
Site Status
RECRUITING
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, United States
Site Status
RECRUITING
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Site Status
RECRUITING
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Site Status
RECRUITING
Riley Hospital for Children
Indianapolis, Indiana, United States
Site Status
RECRUITING
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, United States
Site Status
RECRUITING
Blank Children's Hospital
Des Moines, Iowa, United States
Site Status
RECRUITING
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Site Status
RECRUITING
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Site Status
RECRUITING
Norton Children's Hospital
Louisville, Kentucky, United States
Site Status
RECRUITING
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Site Status
RECRUITING
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Site Status
RECRUITING
Eastern Maine Medical Center
Bangor, Maine, United States
Site Status
RECRUITING
Maine Children's Cancer Program
Scarborough, Maine, United States
Site Status
RECRUITING
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
Site Status
RECRUITING
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Site Status
RECRUITING
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Site Status
RECRUITING
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Site Status
RECRUITING
Tufts Children's Hospital
Boston, Massachusetts, United States
Site Status
ACTIVE_NOT_RECRUITING
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Site Status
RECRUITING
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Site Status
RECRUITING
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, United States
Site Status
RECRUITING
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Site Status
RECRUITING
Children's Hospital of Michigan
Detroit, Michigan, United States
Site Status
RECRUITING
Henry Ford Health Saint John Hospital
Detroit, Michigan, United States
Site Status
ACTIVE_NOT_RECRUITING
Michigan State University
East Lansing, Michigan, United States
Site Status
ACTIVE_NOT_RECRUITING
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Site Status
RECRUITING
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
Site Status
RECRUITING
Corewell Health Children's
Royal Oak, Michigan, United States
Site Status
RECRUITING
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
Site Status
RECRUITING
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Site Status
RECRUITING
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Site Status
RECRUITING
University of Mississippi Medical Center
Jackson, Mississippi, United States
Site Status
RECRUITING
University of Missouri Children's Hospital
Columbia, Missouri, United States
Site Status
SUSPENDED
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Site Status
RECRUITING
Cardinal Glennon Children's Medical Center
St Louis, Missouri, United States
Site Status
ACTIVE_NOT_RECRUITING
Washington University School of Medicine
St Louis, Missouri, United States
Site Status
RECRUITING
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Site Status
RECRUITING
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
Site Status
RECRUITING
University of Nebraska Medical Center
Omaha, Nebraska, United States
Site Status
RECRUITING
University Medical Center of Southern Nevada
Las Vegas, Nevada, United States
Site Status
SUSPENDED
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States
Site Status
SUSPENDED
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, United States
Site Status
RECRUITING
Summerlin Hospital Medical Center
Las Vegas, Nevada, United States
Site Status
RECRUITING
Renown Regional Medical Center
Reno, Nevada, United States
Site Status
RECRUITING
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States
Site Status
RECRUITING
Hackensack University Medical Center
Hackensack, New Jersey, United States
Site Status
RECRUITING
Morristown Medical Center
Morristown, New Jersey, United States
Site Status
RECRUITING
Saint Peter's University Hospital
New Brunswick, New Jersey, United States
Site Status
RECRUITING
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Site Status
RECRUITING
Newark Beth Israel Medical Center
Newark, New Jersey, United States
Site Status
RECRUITING
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States
Site Status
RECRUITING
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Site Status
RECRUITING
Albany Medical Center
Albany, New York, United States
Site Status
RECRUITING
Maimonides Medical Center
Brooklyn, New York, United States
Site Status
RECRUITING
Roswell Park Cancer Institute
Buffalo, New York, United States
Site Status
RECRUITING
NYU Langone Hospital - Long Island
Mineola, New York, United States
Site Status
RECRUITING
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, United States
Site Status
RECRUITING
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Site Status
RECRUITING
Mount Sinai Hospital
New York, New York, United States
Site Status
SUSPENDED
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Site Status
RECRUITING
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Site Status
RECRUITING
NYP/Weill Cornell Medical Center
New York, New York, United States
Site Status
RECRUITING
University of Rochester
Rochester, New York, United States
Site Status
RECRUITING
Stony Brook University Medical Center
Stony Brook, New York, United States
Site Status
RECRUITING
State University of New York Upstate Medical University
Syracuse, New York, United States
Site Status
RECRUITING
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
Site Status
RECRUITING
New York Medical College
Valhalla, New York, United States
Site Status
RECRUITING
Mission Hospital
Asheville, North Carolina, United States
Site Status
RECRUITING
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Site Status
RECRUITING
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Site Status
RECRUITING
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States
Site Status
RECRUITING
Duke University Medical Center
Durham, North Carolina, United States
Site Status
RECRUITING
East Carolina University
Greenville, North Carolina, United States
Site Status
RECRUITING
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Site Status
RECRUITING
Sanford Broadway Medical Center
Fargo, North Dakota, United States
Site Status
RECRUITING
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Site Status
RECRUITING
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Site Status
RECRUITING
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Site Status
RECRUITING
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Site Status
RECRUITING
Nationwide Children's Hospital
Columbus, Ohio, United States
Site Status
RECRUITING
Dayton Children's Hospital
Dayton, Ohio, United States
Site Status
RECRUITING
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, United States
Site Status
RECRUITING
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Site Status
RECRUITING
Legacy Emanuel Children's Hospital
Portland, Oregon, United States
Site Status
RECRUITING
Oregon Health and Science University
Portland, Oregon, United States
Site Status
RECRUITING
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, United States
Site Status
RECRUITING
Geisinger Medical Center
Danville, Pennsylvania, United States
Site Status
RECRUITING
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Site Status
RECRUITING
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Site Status
RECRUITING
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
Site Status
RECRUITING
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Site Status
RECRUITING
Rhode Island Hospital
Providence, Rhode Island, United States
Site Status
RECRUITING
Medical University of South Carolina
Charleston, South Carolina, United States
Site Status
RECRUITING
Prisma Health Richland Hospital
Columbia, South Carolina, United States
Site Status
RECRUITING
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Site Status
RECRUITING
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
Site Status
RECRUITING
T C Thompson Children's Hospital
Chattanooga, Tennessee, United States
Site Status
RECRUITING
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Site Status
RECRUITING
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, United States
Site Status
RECRUITING
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Site Status
RECRUITING
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
Site Status
RECRUITING
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Site Status
RECRUITING
Medical City Dallas Hospital
Dallas, Texas, United States
Site Status
RECRUITING
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Site Status
RECRUITING
El Paso Children's Hospital
El Paso, Texas, United States
Site Status
RECRUITING
Cook Children's Medical Center
Fort Worth, Texas, United States
Site Status
RECRUITING
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Site Status
RECRUITING
M D Anderson Cancer Center
Houston, Texas, United States
Site Status
RECRUITING
Children's Hospital of San Antonio
San Antonio, Texas, United States
Site Status
RECRUITING
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Site Status
RECRUITING
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Site Status
RECRUITING
Scott and White Memorial Hospital
Temple, Texas, United States
Site Status
RECRUITING
Primary Children's Hospital
Salt Lake City, Utah, United States
Site Status
RECRUITING
University of Vermont and State Agricultural College
Burlington, Vermont, United States
Site Status
RECRUITING
University of Virginia Cancer Center
Charlottesville, Virginia, United States
Site Status
RECRUITING
Inova Fairfax Hospital
Falls Church, Virginia, United States
Site Status
RECRUITING
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Site Status
RECRUITING
Naval Medical Center - Portsmouth
Portsmouth, Virginia, United States
Site Status
RECRUITING
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Site Status
RECRUITING
Carilion Children's
Roanoke, Virginia, United States
Site Status
RECRUITING
Seattle Children's Hospital
Seattle, Washington, United States
Site Status
RECRUITING
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Site Status
RECRUITING
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Site Status
RECRUITING
Madigan Army Medical Center
Tacoma, Washington, United States
Site Status
RECRUITING
West Virginia University Charleston Division
Charleston, West Virginia, United States
Site Status
RECRUITING
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, United States
Site Status
RECRUITING
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Site Status
RECRUITING
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Site Status
RECRUITING
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Site Status
RECRUITING
Sydney Children's Hospital
Randwick, New South Wales, Australia
Site Status
ACTIVE_NOT_RECRUITING
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Site Status
ACTIVE_NOT_RECRUITING
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Site Status
RECRUITING
Perth Children's Hospital
Perth, Western Australia, Australia
Site Status
ACTIVE_NOT_RECRUITING
Alberta Children's Hospital
Calgary, Alberta, Canada
Site Status
RECRUITING
University of Alberta Hospital
Edmonton, Alberta, Canada
Site Status
RECRUITING
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
Site Status
RECRUITING
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Site Status
RECRUITING
IWK Health Centre
Halifax, Nova Scotia, Canada
Site Status
RECRUITING
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Site Status
RECRUITING
Kingston Health Sciences Centre
Kingston, Ontario, Canada
Site Status
RECRUITING
Children's Hospital
London, Ontario, Canada
Site Status
RECRUITING
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
Site Status
RECRUITING
Hospital for Sick Children
Toronto, Ontario, Canada
Site Status
RECRUITING
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Site Status
RECRUITING
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Site Status
RECRUITING
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, Canada
Site Status
RECRUITING
Jim Pattison Children's Hospital
Saskatoon, Saskatchewan, Canada
Site Status
RECRUITING
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, , Canada
Site Status
RECRUITING
University Pediatric Hospital
San Juan, , Puerto Rico
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
United States
Australia
Canada
Puerto Rico
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
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References
Explore related publications, articles, or registry entries linked to this study.
Leger KJ, Absalon MJ, Demissei BG, Smith AM, Gerbing RB, Alonzo TA, Narayan HK, Hirsch BA, Pollard JA, Razzouk BI, Getz KD, Aplenc R, Kolb EA, Ky B, Cooper TM. Cardiotoxicity of CPX-351 in children and adolescents with relapsed AML: a Children's Oncology Group report. Front Cardiovasc Med. 2024 Jun 14;11:1347547. doi: 10.3389/fcvm.2024.1347547. eCollection 2024.
Reference Type
DERIVED
Leger KJ, Robison N, Narayan HK, Smith AM, Tsega T, Chung J, Daniels A, Chen Z, Englefield V, Demissei BG, Lefebvre B, Morrow G, Dizon I, Gerbing RB, Pabari R, Getz KD, Aplenc R, Pollard JA, Chow EJ, Tang WHW, Border WL, Sachdeva R, Alonzo TA, Kolb EA, Cooper TM, Ky B. Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy. Front Cardiovasc Med. 2023 Dec 1;10:1286241. doi: 10.3389/fcvm.2023.1286241. eCollection 2023.
Reference Type
DERIVED
Andolina JR, Fries C, Boulware R, Vargas A, Fraint E, Barth M, Ambrusko S, Comito M, Monteleone P. Successful Bone Marrow Transplantation With Intensive Post-transplant Intrathecal Chemotherapy for CNS Relapsed AML in 2 Infants. J Pediatr Hematol Oncol. 2022 Jan 1;44(1):e264-e267. doi: 10.1097/MPH.0000000000002151.
Reference Type
DERIVED
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2020-00546
Identifier Type: REGISTRY
Identifier Source: secondary_id
AAML1831
Identifier Type: OTHER
Identifier Source: secondary_id
AAML1831
Identifier Type: OTHER
Identifier Source: secondary_id
AAML1831
Identifier Type: -
Identifier Source: org_study_id