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

Phase 3

Recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Asparaginase Erwinia chrysanthemi; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexrazoxane Hydrochloride; Drug: Etoposide; Other: Fludeoxyglucose F-18; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Drug: Gemtuzumab Ozogamicin; Procedure: Magnetic Resonance Imaging; Drug: Gilteritinib Fumarate; Drug: Methotrexate; Procedure: Positron Emission Tomography; Drug: Mitoxantrone Hydrochloride; Other: Questionnaire Administration; Drug: Therapeutic Hydrocortisone

• Registration Number: NCT04293562
• Lead Sponsor: Children's Oncology Group

Brief Summary

This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-02-18
• Study First Submitted QC: 2020-03-02
• Study First Posted: 2020-03-03
• Study Start: 2020-07-21
• Status Verified: 2025-05
• Last Update Submitted: 2025-07-09
• Last Update Posted: 2025-07-10
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1186

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A High Risk Group	Questionnaire Administration	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Therapeutic Hydrocortisone	Arm A High Risk Group: See Detailed Description.
Arm A Low Risk Group 1	Asparaginase Erwinia chrysanthemi	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Biospecimen Collection	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Bone Marrow Aspiration	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Bone Marrow Biopsy	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Computed Tomography	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Cytarabine	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Daunorubicin Hydrochloride	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Dexrazoxane Hydrochloride	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Etoposide	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Fludeoxyglucose F-18	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Gemtuzumab Ozogamicin	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Magnetic Resonance Imaging	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Methotrexate	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Positron Emission Tomography	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Questionnaire Administration	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 1	Therapeutic Hydrocortisone	Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A Low Risk Group 2	Asparaginase Erwinia chrysanthemi	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Biospecimen Collection	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Bone Marrow Aspiration	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Bone Marrow Biopsy	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Computed Tomography	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Cytarabine	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Daunorubicin Hydrochloride	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Dexrazoxane Hydrochloride	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Etoposide	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Fludeoxyglucose F-18	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Gemtuzumab Ozogamicin	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Magnetic Resonance Imaging	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Methotrexate	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Mitoxantrone Hydrochloride	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Positron Emission Tomography	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Questionnaire Administration	Arm A Low Risk Group 2: See Detailed Description.
Arm A Low Risk Group 2	Therapeutic Hydrocortisone	Arm A Low Risk Group 2: See Detailed Description.
Arm AC High Risk Group	Allogeneic Hematopoietic Stem Cell Transplantation	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Biospecimen Collection	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Bone Marrow Aspiration	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Bone Marrow Biopsy	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Computed Tomography	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Cytarabine	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Daunorubicin Hydrochloride	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Dexrazoxane Hydrochloride	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Etoposide	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Fludeoxyglucose F-18	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Gemtuzumab Ozogamicin	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Gilteritinib Fumarate	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Magnetic Resonance Imaging	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Methotrexate	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Positron Emission Tomography	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Questionnaire Administration	Arm AC High Risk Group: See Detailed Description.
Arm AC High Risk Group	Therapeutic Hydrocortisone	Arm AC High Risk Group: See Detailed Description.
Arm AC Low Risk Group 2	Asparaginase Erwinia chrysanthemi	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Biospecimen Collection	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Bone Marrow Aspiration	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Bone Marrow Biopsy	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Computed Tomography	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Cytarabine	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Daunorubicin Hydrochloride	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Dexrazoxane Hydrochloride	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Etoposide	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Fludeoxyglucose F-18	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Gemtuzumab Ozogamicin	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Gilteritinib Fumarate	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Magnetic Resonance Imaging	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Methotrexate	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Mitoxantrone Hydrochloride	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Positron Emission Tomography	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Questionnaire Administration	Arm AC Low Risk Group 2: See Detailed Description.
Arm AC Low Risk Group 2	Therapeutic Hydrocortisone	Arm AC Low Risk Group 2: See Detailed Description.
Arm AD High Risk Group	Allogeneic Hematopoietic Stem Cell Transplantation	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Biospecimen Collection	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Bone Marrow Aspiration	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Bone Marrow Biopsy	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Computed Tomography	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Cytarabine	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Daunorubicin Hydrochloride	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Dexrazoxane Hydrochloride	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Etoposide	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Fludeoxyglucose F-18	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Gemtuzumab Ozogamicin	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Gilteritinib Fumarate	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Magnetic Resonance Imaging	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Methotrexate	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Positron Emission Tomography	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Questionnaire Administration	Arm AD High Risk Group: See Detailed Description.
Arm AD High Risk Group	Therapeutic Hydrocortisone	Arm AD High Risk Group: See Detailed Description.
Arm AD Low Risk Group 2	Asparaginase Erwinia chrysanthemi	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Biospecimen Collection	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Bone Marrow Aspiration	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Bone Marrow Biopsy	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Computed Tomography	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Cytarabine	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Daunorubicin Hydrochloride	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Dexrazoxane Hydrochloride	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Etoposide	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Fludeoxyglucose F-18	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Gemtuzumab Ozogamicin	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Gilteritinib Fumarate	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Magnetic Resonance Imaging	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Methotrexate	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Mitoxantrone Hydrochloride	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Positron Emission Tomography	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Questionnaire Administration	Arm AD Low Risk Group 2: See Detailed Description.
Arm AD Low Risk Group 2	Therapeutic Hydrocortisone	Arm AD Low Risk Group 2: See Detailed Description.
Arm B High Risk Group	Allogeneic Hematopoietic Stem Cell Transplantation	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Biospecimen Collection	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Cytarabine	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Bone Marrow Aspiration	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Bone Marrow Biopsy	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Computed Tomography	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Etoposide	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Fludeoxyglucose F-18	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Gemtuzumab Ozogamicin	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Liposome-encapsulated Daunorubicin-Cytarabine	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Magnetic Resonance Imaging	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Methotrexate	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Positron Emission Tomography	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Questionnaire Administration	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B High Risk Group	Therapeutic Hydrocortisone	Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Asparaginase Erwinia chrysanthemi	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Biospecimen Collection	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Bone Marrow Aspiration	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Bone Marrow Biopsy	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Computed Tomography	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Cytarabine	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Etoposide	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Fludeoxyglucose F-18	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Gemtuzumab Ozogamicin	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Liposome-encapsulated Daunorubicin-Cytarabine	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Magnetic Resonance Imaging	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Methotrexate	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Positron Emission Tomography	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Questionnaire Administration	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 1	Therapeutic Hydrocortisone	Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Asparaginase Erwinia chrysanthemi	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Biospecimen Collection	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Bone Marrow Aspiration	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Bone Marrow Biopsy	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Computed Tomography	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Cytarabine	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Etoposide	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Fludeoxyglucose F-18	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Gemtuzumab Ozogamicin	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Liposome-encapsulated Daunorubicin-Cytarabine	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Methotrexate	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Mitoxantrone Hydrochloride	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Positron Emission Tomography	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Questionnaire Administration	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm B Low Risk Group 2	Therapeutic Hydrocortisone	Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Allogeneic Hematopoietic Stem Cell Transplantation	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Biospecimen Collection	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Bone Marrow Aspiration	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Bone Marrow Biopsy	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Computed Tomography	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Cytarabine	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Etoposide	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Fludeoxyglucose F-18	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Gemtuzumab Ozogamicin	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Gilteritinib Fumarate	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Liposome-encapsulated Daunorubicin-Cytarabine	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Magnetic Resonance Imaging	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Methotrexate	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Positron Emission Tomography	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Questionnaire Administration	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC High Risk Group	Therapeutic Hydrocortisone	Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Asparaginase Erwinia chrysanthemi	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Biospecimen Collection	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Bone Marrow Aspiration	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Bone Marrow Biopsy	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Computed Tomography	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Cytarabine	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Dexrazoxane Hydrochloride	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Etoposide	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Fludeoxyglucose F-18	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Gemtuzumab Ozogamicin	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Gilteritinib Fumarate	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Liposome-encapsulated Daunorubicin-Cytarabine	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Magnetic Resonance Imaging	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Methotrexate	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Mitoxantrone Hydrochloride	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Positron Emission Tomography	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Questionnaire Administration	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BC Low Risk Group 2	Therapeutic Hydrocortisone	Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Allogeneic Hematopoietic Stem Cell Transplantation	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Biospecimen Collection	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Bone Marrow Aspiration	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Bone Marrow Biopsy	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Computed Tomography	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Cytarabine	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Etoposide	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Fludeoxyglucose F-18	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Gemtuzumab Ozogamicin	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Gilteritinib Fumarate	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Liposome-encapsulated Daunorubicin-Cytarabine	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Magnetic Resonance Imaging	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Methotrexate	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Positron Emission Tomography	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Questionnaire Administration	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD High Risk Group	Therapeutic Hydrocortisone	Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Asparaginase Erwinia chrysanthemi	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Biospecimen Collection	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Bone Marrow Aspiration	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Bone Marrow Biopsy	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Computed Tomography	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Cytarabine	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Dexrazoxane Hydrochloride	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Etoposide	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Fludeoxyglucose F-18	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Gemtuzumab Ozogamicin	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Gilteritinib Fumarate	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Liposome-encapsulated Daunorubicin-Cytarabine	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Magnetic Resonance Imaging	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Methotrexate	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Mitoxantrone Hydrochloride	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Positron Emission Tomography	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Questionnaire Administration	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm BD Low Risk Group 2	Therapeutic Hydrocortisone	Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
Arm A High Risk Group	Allogeneic Hematopoietic Stem Cell Transplantation	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Biospecimen Collection	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Bone Marrow Aspiration	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Bone Marrow Biopsy	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Computed Tomography	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Cytarabine	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Daunorubicin Hydrochloride	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Dexrazoxane Hydrochloride	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Etoposide	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Fludeoxyglucose F-18	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Gemtuzumab Ozogamicin	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Magnetic Resonance Imaging	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Methotrexate	Arm A High Risk Group: See Detailed Description.
Arm A High Risk Group	Positron Emission Tomography	Arm A High Risk Group: See Detailed Description.

Primary Outcome Measures

Name	Time	Method
Event-free survival (EFS)	Up to 3 years	The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 3 years	The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
Proportion of patients positive for minimal residual disease (MRD+)	Up to 4 weeks	The proportion of patients MRD+ at end of induction 1 (EOI1) will be estimated as the number of patients MRD+ divided by the number of patients with evaluable EOI1 MRD results along with a corresponding 95% confidence interval determined using a binomial exact method.
Proportion of patients who died during protocol therapy	Up to 2 years	The proportion of patients who died during protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method.
Incidence of adverse events	Up to 2 years	The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 5.0.
Relapse rate	Up to 3 years	Cumulative incidence estimates will be used to determine the 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events.
Treatment-related mortality rate (TRM)	Up to 3 years	Cumulative incidence estimates will be used to determine the 3 year TRM defined as time from study entry to death where induction failure, relapse or secondary malignancies are competing events.
Number of patients who undergo hematopoietic stem cell transplant (HSCT)	Up to 3 years

Trial Locations

Locations (205)

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

USA Health Strada Patient Care Center; 🇺🇸 Mobile, Alabama, United States

Banner Children's at Desert; 🇺🇸 Mesa, Arizona, United States

Phoenix Childrens Hospital; 🇺🇸 Phoenix, Arizona, United States

Banner University Medical Center - Tucson; 🇺🇸 Tucson, Arizona, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center; 🇺🇸 Downey, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Miller Children's and Women's Hospital Long Beach; 🇺🇸 Long Beach, California, United States

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