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

• ClinicalTrials.gov Identifier: NCT04293562
• Recruitment Status: Recruiting
• First Posted: March 3, 2020
• Last Update Posted: May 4, 2022
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Asparaginase; Drug: Asparaginase Erwinia chrysanthemi; Behavioral: Cogstate Assessment Battery; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexrazoxane Hydrochloride; Drug: Etoposide; Drug: Gemtuzumab Ozogamicin; Drug: Gilteritinib Fumarate; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Drug: Methotrexate; Drug: Mitoxantrone Hydrochloride; Drug: Therapeutic Hydrocortisone	Phase 3

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 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.

Risk group assignments are calculated based on cytogenetic, molecular and genomic findings (details in protocol)

Risk groups include (Details in protocol):

1. Low Risk 1 (LR1)
2. Low Risk 2 (LR2)

3. High Risk (HR)

   TREATMENT FOR PATIENTS WITHOUT FLT3 MUTATIONS:

   ARM A LOW RISK GROUP 1:

   INDUCTION 1: Patients receive cytarabine intravenously (IV) over 1-30 minutes every 12 hours (Q12H) on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate intrathecally (IT), therapeutic hydrocortisone (hydrocortisone) IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT once weekly (QW) starting on day 8 for 4-6 weeks (may continue into Induction 2) until the cerebral spinal fluid (CSF) is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5.

   INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.

   INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi intramuscularly (IM) or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.

   ARM B LOW RISK GROUP 1:

   INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5.

   INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.

   INTENSIFICATION 2: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.

   ARM A LOW RISK GROUP 2:

   INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5.

   INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.

   INTENSIFICATION 2: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4 and dexrazoxane IV over 5-15 minutes and mitoxantrone hydrochloride (mitoxantrone) IV over 5-15 minutes on days 3-6.

   INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.

   ARM B LOW RISK GROUP 2:

   INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5.

   INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.

   INTENSIFICATION 2: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4 and dexrazoxane IV over 5-15 minutes and mitoxantrone hydrochloride (mitoxantrone) IV over 5-15 minutes on days 3-6.

   INTENSIFICATION 3: Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9. Patients also receive asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9.

   ARM A HIGH RISK GROUP:

   INDUCTION 1: Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8 and dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5.

   INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.

   HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.

   ARM B HIGH RISK GROUP:

   INDUCTION 1: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2: Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5.

   INTENSIFICATION 1: Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5.

   HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.

   TREATMENT FOR PATIENTS WITH FLT3/ITD MUTATIONS (ITD AR > 0.1):

   ARM AC LOW RISK GROUP 2:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.

   INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.

   POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via nasogastric (NG) or gastronomy (G) tube daily on days 1-365.

   ARM BC LOW RISK GROUP 2:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.

   INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.

   POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   ARM AC HIGH RISK GROUP:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.

   POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   ARM BC HIGH RISK GROUP:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.

   POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   TREATMENT FOR NON-ITD FLT3 ACTIVATING MUTATIONS:

   ARM AD LOW RISK GROUP 2:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.

   INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.

   POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   ARM BD LOW RISK GROUP 2:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   INTENSIFICATION 2 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H on days 1-4, dexrazoxane IV over 5-15 minutes and mitoxantrone IV over 5-15 minutes on days 3-6, and gilteritinib PO QD on days 7-34.

   INTENSIFICATION 3 (WITH GILTERITINIB): Patients receive high-dose cytarabine IV over 3 hours Q12H on days 1, 2, 8, and 9, asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9, and gilteritinib PO QD on days 10-37.

   POST-CHEMOTHERAPY GILTERITINIB MAINTENANCE: Patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   ARM AD HIGH RISK GROUP:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive cytarabine IV over 1-30 minutes Q12H on days 1-10, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib orally (PO) once daily (QD) on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive cytarabine IV over 1-30 minutes Q12H on days 1-8, dexrazoxane IV over 5-15 minutes and daunorubicin IV over 1-15 minutes on days 1, 3, and 5, and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.

   POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   ARM BD HIGH RISK GROUP:

   CONTINUED INDUCTION 1 (WITH GILTERITINIB): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, gemtuzumab ozogamicin IV over 2 hours on day 6, and gilteritinib PO QD on days 11-31. Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 8. Patients with CNS2, CNS3a, and CNS3b receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 8 for 4-6 weeks (may continue into Induction 2) until the CSF is clear of blasts (CNS1 status). Patients with CNS3c receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 1 for 6 weeks (may continue into Induction 2).

   INDUCTION 2 (WITH GILTERITINIB): Patients with CNS1 receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients with CNS2 receive methotrexate IT, hydrocortisone IT, and cytarabine IT QW starting on day 0 until CNS1 status is reached. Patients also receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and gilteritinib PO QD on days 11-38.

   INTENSIFICATION 1 (WITH GILTERITINIB): Patients receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 0. Patients also receive high-dose cytarabine IV over 1-3 hours Q12H and etoposide IV over 90-120 minutes on days 1-5, and gilteritinib PO QD on days 6-33.

   HSCT: After completion of Intensification 1 and investigator assigned conditioning regimen, patients undergo allogeneic HSCT.

   POST-HSCT GILTERITINIB MAINTENANCE: Beginning 30-120 days after completion of HSCT, patients receive gilteritinib PO QD or via NG or G tube daily on days 1-365.

   NOTE: During Induction 2 or Intensification 2, patients in Arms A and B with left ventricular systolic dysfunction receive a replacement course of high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9, and asparaginase Erwinia chrysanthemi IM or IV over 1-2 hours and asparaginase IM or IV over 30 minutes on days 2 and 9. Patients in Arms AC, BC, AD, and BD receive treatment as in Arms A and B and also receive gilteritinib PO QD on days 10-37 (Induction 2) or days 10-37 (Intensification 2).

   All treatment continues in the absence of disease progression or unacceptable toxicity.

   OPTIONAL NEUROCOGNITIVE STUDY:

   Patients may complete the Cogstate assessment battery at the end of Induction 1, at the end of therapy, and at 9 and 60 months post-enrollment.

   After completion of study treatment, patients are followed up monthly for 6 months and then every other mon

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations
• Actual Study Start Date: July 20, 2020
• Estimated Primary Completion Date: September 30, 2027
• Estimated Study Completion Date: September 30, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A High Risk Group; Arm A High Risk Group: See Detailed Description.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm A Low Risk Group 1; Arm A Low Risk Group 1: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm A Low Risk Group 2; Arm A Low Risk Group 2: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm AC High Risk Group; Arm AC High Risk Group: See Detailed Description.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm AC Low Risk Group 2; Arm AC Low Risk Group 2: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm AD High Risk Group; Arm AD High Risk Group: See Detailed Description.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm AD Low Risk Group 2; Arm AD Low Risk Group 2: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm B High Risk Group; Arm B High Risk Group: See Detailed Description.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm B Low Risk Group 1; Arm B Low Risk Group 1: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm B Low Risk Group 2; Arm B Low Risk Group 2: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm BC High Risk Group; Arm BC High Risk Group: See Detailed Description.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm BC Low Risk Group 2; Arm BC Low Risk Group 2: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm BD High Risk Group; Arm BD High Risk Group: See Detailed Description.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo allogeneic HSCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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
Experimental: Arm BD Low Risk Group 2; Arm BD Low Risk Group 2: See Detailed Description.	Drug: Asparaginase; Given IM or IV; Other Names: ASP-1; Asparaginase II; Asparaginase-E.Coli; Colaspase; Elspar; Kidrolase; L-Asnase; L-ASP; L-Asparaginase; L-Asparagine Amidohydrolase; Laspar; Lcf-ASP; Leucogen; Leunase; MK-965; Paronal; Re-82-TAD-15; Serasa; Spectrila; Drug: Asparaginase Erwinia chrysanthemi; Given IM or IV; Other Names: Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; L-asparginase (Erwinia ); Behavioral: Cogstate Assessment Battery; Ancillary studies; Drug: Cytarabine; Given IV or IT; Other Names: .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; Drug: Dexrazoxane Hydrochloride; Given IV; Other Names: Cardioxane; Totect; Zinecard; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Gemtuzumab Ozogamicin; Given IV; Other Names: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody; CDP-771; CMA-676; gemtuzumab; hP67.6-Calicheamicin; Mylotarg; WAY-CMA-676; Drug: Gilteritinib Fumarate; Given PO or via NG or G tube; Other Names: ASP-2215 Hemifumarate; ASP2215 Hemifumarate; Gilteritinib Hemifumarate; Xospata; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; 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; Drug: Methotrexate; Given IT; Other Names: Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; 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; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Drug: Therapeutic Hydrocortisone; Given IT; Other Names: 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

Outcome Measures

Primary Outcome Measures :

1. Event-free survival (EFS) [ Time Frame: 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 :

1. Overall survival (OS) [ Time Frame: 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.
2. Proportion of patients positive for minimal residual disease (MRD+) [ Time Frame: 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.
3. Proportion of patients who died during protocol therapy [ Time Frame: 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.
4. Relapse rate [ Time Frame: 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.
5. Treatment-related mortality rate (TRM) [ Time Frame: 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.
6. Incidence of adverse events [ Time Frame: Up to 2 years ]
   The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

Other Outcome Measures:

1. Course duration [ Time Frame: Up to 2 years ]
   Median and range of the length of course duration will be determined.
2. Length of hospitalization [ Time Frame: Up to 2 years ]
   Median and range of the length of hospitalization time during protocol therapy will be determined.
3. Time to count recovery [ Time Frame: Up to 2 years ]
   Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery in days where deaths are competing events.

Eligibility Criteria

• Ages Eligible for Study: up to 22 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures
• Patients must be less than 22 years of age at the time of study enrollment

• Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease

  • Patient must have 1 of the following:

    • >= 20% bone marrow blasts (obtained within 14 days prior to enrollment)

      • In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
    • < 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
    • A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
• ARM C: Patient must be >= 2 years of age at the time of Late Callback
• ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology
• ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
• ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
• ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
• ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
• ARM D: Patient must be >= 2 years of age at the time of Late Callback
• ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
• ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
• ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
• ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
• NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
• NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
• NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
• NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
• NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion Criteria:

• Fanconi anemia
• Shwachman Diamond syndrome
• Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
• Telomere disorders
• Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
• Any concurrent malignancy
• Juvenile myelomonocytic leukemia (JMML)
• Philadelphia chromosome positive AML
• Mixed phenotype acute leukemia
• Acute promyelocytic leukemia
• Acute myeloid leukemia arising from myelodysplasia
• Therapy-related myeloid neoplasms
• Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) < 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen

• Administration of prior anti-cancer therapy except as outlined below:

  • Hydroxyurea
  • All-trans retinoic acid (ATRA)
  • Corticosteroids (any route)
  • Intrathecal therapy given at diagnosis
  • In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• ARM D: Patient does not have any congenital long QT syndrome or congenital heart block

Contacts and Locations

Locations

United States, Alabama

Children's Hospital of Alabama; Recruiting

Birmingham, Alabama, United States, 35233

Contact: Site Public Contact 205-638-9285 oncologyresearch@peds.uab.edu

Principal Investigator: Matthew A. Kutny

USA Health Strada Patient Care Center; Recruiting

Mobile, Alabama, United States, 36604

Contact: Site Public Contact 800-388-8721

Principal Investigator: Hamayun Imran

United States, Arizona

Banner Children's at Desert; Recruiting

Mesa, Arizona, United States, 85202

Contact: Site Public Contact 480-412-3100

Principal Investigator: Joseph C. Torkildson

Phoenix Childrens Hospital; Recruiting

Phoenix, Arizona, United States, 85016

Contact: Site Public Contact 602-546-0920

Principal Investigator: Dana B. Salzberg

Banner University Medical Center - Tucson; Recruiting

Tucson, Arizona, United States, 85719

Contact: Site Public Contact UACC-NCTN@uacc.arizona.edu

Principal Investigator: Holly E. Pariury

United States, Arkansas

Arkansas Children's Hospital; Recruiting

Little Rock, Arkansas, United States, 72202-3591

Contact: Site Public Contact 501-364-7373

Principal Investigator: David L. Becton

United States, California

Kaiser Permanente Downey Medical Center; Recruiting

Downey, California, United States, 90242

Contact: Site Public Contact 626-564-3455

Principal Investigator: Robert M. Cooper

City of Hope Comprehensive Cancer Center; Recruiting

Duarte, California, United States, 91010

Contact: Site Public Contact 800-826-4673 becomingapatient@coh.org

Principal Investigator: Anna B. Pawlowska

Loma Linda University Medical Center; Recruiting

Loma Linda, California, United States, 92354

Contact: Site Public Contact 909-558-4050

Principal Investigator: Albert Kheradpour

Miller Children's and Women's Hospital Long Beach; Recruiting

Long Beach, California, United States, 90806

Contact: Site Public Contact 562-933-5600

Principal Investigator: Jacqueline N. Casillas

Children's Hospital Los Angeles; Recruiting

Los Angeles, California, United States, 90027

Contact: Site Public Contact 323-361-4110

Principal Investigator: Leo Mascarenhas

Cedars Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Contact: Site Public Contact 310-423-8965

Principal Investigator: Fataneh (Fae) Majlessipour

Mattel Children's Hospital UCLA; Recruiting

Los Angeles, California, United States, 90095

Contact: Site Public Contact 310-825-6708

Principal Investigator: William A. May

UCSF Benioff Children's Hospital Oakland; Recruiting

Oakland, California, United States, 94609

Contact: Site Public Contact 510-428-3324 Carla.Golden@ucsf.edu

Principal Investigator: Carla B. Golden

Kaiser Permanente-Oakland; Recruiting

Oakland, California, United States, 94611

Contact: Site Public Contact 877-642-4691 Kpoct@kp.org

Principal Investigator: Aarati V. Rao

Children's Hospital of Orange County; Recruiting

Orange, California, United States, 92868

Contact: Site Public Contact 714-509-8646 oncresearch@choc.org

Principal Investigator: Elyssa M. Rubin

University of California Davis Comprehensive Cancer Center; Recruiting

Sacramento, California, United States, 95817

Contact: Site Public Contact 916-734-3089

Principal Investigator: Marcio H. Malogolowkin

Rady Children's Hospital - San Diego; Recruiting

San Diego, California, United States, 92123

Contact: Site Public Contact 858-966-5934

Principal Investigator: William D. Roberts

UCSF Medical Center-Mission Bay; Recruiting

San Francisco, California, United States, 94158

Contact: Site Public Contact 877-827-3222

Principal Investigator: Benjamin J. Huang

Santa Barbara Cottage Hospital; Recruiting

Santa Barbara, California, United States, 93102

Contact: Site Public Contact 805-682-7300

Principal Investigator: David J. Slomiany

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Site Public Contact 303-764-5056 josh.b.gordon@nsmtp.kp.org

Principal Investigator: Kelly W. Maloney

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center; Recruiting

Denver, Colorado, United States, 80218

Contact: Site Public Contact 303-839-6000

Principal Investigator: Jennifer J. Clark

United States, Connecticut

Connecticut Children's Medical Center; Recruiting

Hartford, Connecticut, United States, 06106

Contact: Site Public Contact 860-545-9981

Principal Investigator: Michael S. Isakoff

Yale University; Recruiting

New Haven, Connecticut, United States, 06520

Contact: Site Public Contact 203-785-5702 canceranswers@yale.edu

Principal Investigator: Farzana Pashankar

United States, Delaware

Alfred I duPont Hospital for Children; Recruiting

Wilmington, Delaware, United States, 19803

Contact: Site Public Contact 302-651-6884 dperry@nemours.org

Principal Investigator: Emi H. Caywood

United States, District of Columbia

MedStar Georgetown University Hospital; Recruiting

Washington, District of Columbia, United States, 20007

Contact: Site Public Contact 202-444-2223

Principal Investigator: Nina S. Kadan-Lottick

Children's National Medical Center; Recruiting

Washington, District of Columbia, United States, 20010

Contact: Site Public Contact 202-884-2549

Principal Investigator: Jeffrey S. Dome

United States, Florida

Broward Health Medical Center; Recruiting

Fort Lauderdale, Florida, United States, 33316

Contact: Site Public Contact 954-355-5346

Principal Investigator: Hector M. Rodriguez-Cortes

Golisano Children's Hospital of Southwest Florida; Recruiting

Fort Myers, Florida, United States, 33908

Contact: Site Public Contact 239-343-5333 molly.arnstrom@leehealth.org

Principal Investigator: Emad K. Salman

University of Florida Health Science Center - Gainesville; Recruiting

Gainesville, Florida, United States, 32610

Contact: Site Public Contact 352-273-8010 cancer-center@ufl.edu

Principal Investigator: William B. Slayton

Memorial Regional Hospital/Joe DiMaggio Children's Hospital; Recruiting

Hollywood, Florida, United States, 33021

Contact: Site Public Contact 954-265-1847 OHR@mhs.net

Principal Investigator: Iftikhar Hanif

Nemours Children's Clinic-Jacksonville; Recruiting

Jacksonville, Florida, United States, 32207

Contact: Site Public Contact 904-697-3529

Principal Investigator: Emi H. Caywood

Palms West Radiation Therapy; Recruiting

Loxahatchee Groves, Florida, United States, 33470

Contact: Site Public Contact helpdesk@childrensoncologygroup.org

Principal Investigator: Melissa S. Singer

University of Miami Miller School of Medicine-Sylvester Cancer Center; Recruiting

Miami, Florida, United States, 33136

Contact: Site Public Contact 305-243-2647

Principal Investigator: Julio C. Barredo

Nicklaus Children's Hospital; Recruiting

Miami, Florida, United States, 33155

Contact: Site Public Contact 888-624-2778

Principal Investigator: Enrique A. Escalon

AdventHealth Orlando; Recruiting

Orlando, Florida, United States, 32803

Contact: Site Public Contact 407-303-2090 FH.Cancer.Research@flhosp.org

Principal Investigator: Fouad M. Hajjar

Arnold Palmer Hospital for Children; Recruiting

Orlando, Florida, United States, 32806

Contact: Site Public Contact 321-841-2008 melissa.leffin@orlandohealth.com

Principal Investigator: Amy A. Smith

Nemours Children's Hospital; Recruiting

Orlando, Florida, United States, 32827

Contact: Site Public Contact 407-650-7715

Principal Investigator: Emi H. Caywood

Sacred Heart Hospital; Recruiting

Pensacola, Florida, United States, 32504

Contact: Site Public Contact 850-416-4611 eebrou@ascension.org

Principal Investigator: Erlyn C. Smith

Johns Hopkins All Children's Hospital; Recruiting

Saint Petersburg, Florida, United States, 33701

Contact: Site Public Contact 727-767-4784 Ashley.Repp@jhmi.edu

Principal Investigator: Jennifer L. Mayer

Tampa General Hospital; Recruiting

Tampa, Florida, United States, 33606

Contact: Site Public Contact 813-844-7829 syapchanyk@tgh.org

Principal Investigator: Juan F. Rico

Saint Joseph's Hospital/Children's Hospital-Tampa; Recruiting

Tampa, Florida, United States, 33607

Contact: Site Public Contact 813-357-0849 jennifer.manns@baycare.org

Principal Investigator: Don E. Eslin

Saint Mary's Hospital; Recruiting

West Palm Beach, Florida, United States, 33407

Contact: Site Public Contact 561-881-2815

Principal Investigator: Narayana Gowda

United States, Georgia

Children's Healthcare of Atlanta - Egleston; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Site Public Contact 404-785-2025 Leann.Schilling@choa.org

Principal Investigator: Himalee S. Sabnis

Augusta University Medical Center; Recruiting

Augusta, Georgia, United States, 30912

Contact: Site Public Contact 706-721-2388 ga_cares@augusta.edu

Principal Investigator: Colleen H. McDonough

Memorial Health University Medical Center; Recruiting

Savannah, Georgia, United States, 31404

Contact: Site Public Contact 912-350-7887 Lorraine.OHara@hcahealthcare.com

Principal Investigator: Andrew L. Pendleton

United States, Hawaii

Kapiolani Medical Center for Women and Children; Recruiting

Honolulu, Hawaii, United States, 96826

Contact: Site Public Contact 808-983-6090

Principal Investigator: Wade T. Kyono

United States, Idaho

Saint Luke's Cancer Institute - Boise; Recruiting

Boise, Idaho, United States, 83712

Contact: Site Public Contact 208-381-2774 eslinget@slhs.org

Principal Investigator: Eugenia Chang

United States, Illinois

Lurie Children's Hospital-Chicago; Recruiting

Chicago, Illinois, United States, 60611

Contact: Site Public Contact 773-880-4562

Principal Investigator: Jenna Rossoff

University of Illinois; Recruiting

Chicago, Illinois, United States, 60612

Contact: Site Public Contact 312-355-3046

Principal Investigator: Mary L. Schmidt

Loyola University Medical Center; Recruiting

Maywood, Illinois, United States, 60153

Contact: Site Public Contact 708-226-4357

Principal Investigator: Eugene Suh

Advocate Children's Hospital-Oak Lawn; Recruiting

Oak Lawn, Illinois, United States, 60453

Contact: Site Public Contact 847-723-7570

Principal Investigator: Rebecca E. McFall

Advocate Children's Hospital-Park Ridge; Recruiting

Park Ridge, Illinois, United States, 60068

Contact: Site Public Contact helpdesk@childrensoncologygroup.org

Principal Investigator: Rebecca E. McFall

Saint Jude Midwest Affiliate; Recruiting

Peoria, Illinois, United States, 61637

Contact: Site Public Contact 888-226-4343

Principal Investigator: Jaime M. Libes

Southern Illinois University School of Medicine; Recruiting

Springfield, Illinois, United States, 62702

Contact: Site Public Contact 217-545-7929

Principal Investigator: Gregory P. Brandt

United States, Indiana

Riley Hospital for Children; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Site Public Contact 800-248-1199

Principal Investigator: Sandeep Batra

Saint Vincent Hospital and Health Care Center; Recruiting

Indianapolis, Indiana, United States, 46260

Contact: Site Public Contact 317-338-2194 research@stvincent.org

Principal Investigator: Bassem I. Razzouk

United States, Iowa

Blank Children's Hospital; Recruiting

Des Moines, Iowa, United States, 50309

Contact: Site Public Contact 515-241-8912 samantha.mallory@unitypoint.org

Principal Investigator: Samantha L. Mallory

University of Iowa/Holden Comprehensive Cancer Center; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Site Public Contact 800-237-1225

Principal Investigator: David S. Dickens

United States, Kentucky

University of Kentucky/Markey Cancer Center; Recruiting

Lexington, Kentucky, United States, 40536

Contact: Site Public Contact 859-257-3379

Principal Investigator: James T. Badgett

Norton Children's Hospital; Recruiting

Louisville, Kentucky, United States, 40202

Contact: Site Public Contact 502-629-5500 CancerResource@nortonhealthcare.org

Principal Investigator: Ashok B. Raj

United States, Louisiana

Children's Hospital New Orleans; Recruiting

New Orleans, Louisiana, United States, 70118

Contact: Site Public Contact CHResearch@lcmchealth.org

Principal Investigator: Lolie C. Yu

Ochsner Medical Center Jefferson; Recruiting

New Orleans, Louisiana, United States, 70121

Contact: Site Public Contact 504-842-8084 Elisemarie.curry@ochsner.org

Principal Investigator: Craig Lotterman

United States, Maine

Maine Children's Cancer Program; Recruiting

Scarborough, Maine, United States, 04074

Contact: Site Public Contact 207-396-7581 sverwys@mmc.org

Principal Investigator: Eric C. Larsen

United States, Maryland

University of Maryland/Greenebaum Cancer Center; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Site Public Contact 800-888-8823

Principal Investigator: Teresa A. York

Sinai Hospital of Baltimore; Recruiting

Baltimore, Maryland, United States, 21215

Contact: Site Public Contact 410-601-6120 pridgely@lifebridgehealth.org

Principal Investigator: Jason M. Fixler

Johns Hopkins University/Sidney Kimmel Cancer Center; Recruiting

Baltimore, Maryland, United States, 21287

Contact: Site Public Contact 410-955-8804 jhcccro@jhmi.edu

Principal Investigator: Alan D. Friedman

Walter Reed National Military Medical Center; Recruiting

Bethesda, Maryland, United States, 20889-5600

Contact: Site Public Contact 301-319-2100

Principal Investigator: Rebecca O. Clark

United States, Massachusetts

Tufts Children's Hospital; Recruiting

Boston, Massachusetts, United States, 02111

Contact: Site Public Contact 617-636-5535

Principal Investigator: Jason Law

Massachusetts General Hospital Cancer Center; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Site Public Contact 877-726-5130

Principal Investigator: Howard J. Weinstein

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Site Public Contact 877-442-3324

Principal Investigator: Jessica A. Pollard

UMass Memorial Medical Center - University Campus; Recruiting

Worcester, Massachusetts, United States, 01655

Contact: Site Public Contact 508-856-3216 cancer.research@umassmed.edu

Principal Investigator: Stefanie R. Lowas

United States, Michigan

C S Mott Children's Hospital; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Site Public Contact 800-865-1125

Principal Investigator: Laura Sedig

Ascension Saint John Hospital; Recruiting

Detroit, Michigan, United States, 48236

Contact: Site Public Contact 313-343-3166 karen.forman@ascension.org

Principal Investigator: Adonis N. Lorenzana

Michigan State University Clinical Center; Recruiting

East Lansing, Michigan, United States, 48824-7016

Contact: Site Public Contact 517-975-9547

Principal Investigator: Laura E. Agresta

Helen DeVos Children's Hospital at Spectrum Health; Recruiting

Grand Rapids, Michigan, United States, 49503

Contact: Site Public Contact 616-391-1230 crcwm-regulatory@crcwm.org

Principal Investigator: Kathleen J. Yost

Bronson Methodist Hospital; Recruiting

Kalamazoo, Michigan, United States, 49007

Contact: Site Public Contact 616-391-1230 crcwm-regulatory@crcwm.org

Principal Investigator: Kathleen J. Yost

Beaumont Children's Hospital-Royal Oak; Recruiting

Royal Oak, Michigan, United States, 48073

Contact: Site Public Contact 248-551-7695

Principal Investigator: Laura K. Gowans

United States, Minnesota

Children's Hospitals and Clinics of Minnesota - Minneapolis; Recruiting

Minneapolis, Minnesota, United States, 55404

Contact: Site Public Contact 612-813-5193

Principal Investigator: Michael K. Richards

University of Minnesota/Masonic Cancer Center; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Site Public Contact 612-624-2620

Principal Investigator: Peter M. Gordon

Mayo Clinic in Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Site Public Contact 855-776-0015

Principal Investigator: Mira Kohorst

United States, Mississippi

University of Mississippi Medical Center; Recruiting

Jackson, Mississippi, United States, 39216

Contact: Site Public Contact 601-815-6700

Principal Investigator: Anderson (Andy) B. Collier

United States, Missouri

Columbia Regional; Recruiting

Columbia, Missouri, United States, 65201

Contact: Site Public Contact helpdesk@childrensoncologygroup.org

Principal Investigator: Barbara A. Gruner

Children's Mercy Hospitals and Clinics; Recruiting

Kansas City, Missouri, United States, 64108

Contact: Site Public Contact 816-302-6808 rryan@cmh.edu

Principal Investigator: Keith J. August

Cardinal Glennon Children's Medical Center; Recruiting

Saint Louis, Missouri, United States, 63104

Contact: Site Public Contact 314-268-4000

Principal Investigator: William S. Ferguson

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Site Public Contact 800-600-3606 info@siteman.wustl.edu

Principal Investigator: Shalini Shenoy

Mercy Hospital Saint Louis; Recruiting

Saint Louis, Missouri, United States, 63141

Contact: Site Public Contact 314-251-7066

Principal Investigator: Robin D. Hanson

United States, Nebraska

Children's Hospital and Medical Center of Omaha; Recruiting

Omaha, Nebraska, United States, 68114

Contact: Site Public Contact 402-955-3949

Principal Investigator: Jill C. Beck

University of Nebraska Medical Center; Recruiting

Omaha, Nebraska, United States, 68198

Contact: Site Public Contact 402-559-6941 unmcrsa@unmc.edu

Principal Investigator: Jill C. Beck

United States, Nevada

University Medical Center of Southern Nevada; Recruiting

Las Vegas, Nevada, United States, 89102

Contact: Site Public Contact 702-384-0013 research@sncrf.org

Principal Investigator: Alan K. Ikeda

Sunrise Hospital and Medical Center; Recruiting

Las Vegas, Nevada, United States, 89109

Contact: Site Public Contact 702-384-0013 research@sncrf.org

Principal Investigator: Alan K. Ikeda

Alliance for Childhood Diseases/Cure 4 the Kids Foundation; Recruiting

Las Vegas, Nevada, United States, 89135

Contact: Site Public Contact 702-384-0013 research@sncrf.org

Principal Investigator: Alan K. Ikeda

Summerlin Hospital Medical Center; Recruiting

Las Vegas, Nevada, United States, 89144

Contact: Site Public Contact 702-384-0013 research@sncrf.org

Principal Investigator: Alan K. Ikeda

Renown Regional Medical Center; Recruiting

Reno, Nevada, United States, 89502

Contact: Site Public Contact 702-384-0013 research@sncrf.org

Principal Investigator: Alan K. Ikeda

United States, New Hampshire

Dartmouth Hitchcock Medical Center; Recruiting

Lebanon, New Hampshire, United States, 03756

Contact: Site Public Contact 800-639-6918 cancer.research.nurse@dartmouth.edu

Principal Investigator: Julie Kim

United States, New Jersey

Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

Contact: Site Public Contact 201-996-2879

Principal Investigator: Jing Chen

Morristown Medical Center; Recruiting

Morristown, New Jersey, United States, 07960

Contact: Site Public Contact 973-971-5900

Principal Investigator: Kathryn L. Laurie

Saint Peter's University Hospital; Recruiting

New Brunswick, New Jersey, United States, 08901

Contact: Site Public Contact 732-745-8600 ext 6163 kcovert@saintpetersuh.com

Principal Investigator: Nibal A. Zaghloul

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital; Recruiting

New Brunswick, New Jersey, United States, 08903

Contact: Site Public Contact 732-235-8675

Principal Investigator: Richard A. Drachtman

Newark Beth Israel Medical Center; Recruiting

Newark, New Jersey, United States, 07112

Contact: Site Public Contact 973-926-7230 Christine.Kosmides@rwjbh.org

Principal Investigator: Teena Bhatla

Saint Joseph's Regional Medical Center; Recruiting

Paterson, New Jersey, United States, 07503

Contact: Site Public Contact 973-754-2207 HallL@sjhmc.org

Principal Investigator: Alissa Kahn

United States, New York

Albany Medical Center; Recruiting

Albany, New York, United States, 12208

Contact: Site Public Contact 518-262-5513

Principal Investigator: Lauren R. Weintraub

Montefiore Medical Center - Moses Campus; Recruiting

Bronx, New York, United States, 10467

Contact: Site Public Contact 718-379-6866 eskwak@montefiore.org

Principal Investigator: Lisa Gennarini

Maimonides Medical Center; Recruiting

Brooklyn, New York, United States, 11219

Contact: Site Public Contact 718-765-2500

Principal Investigator: Mahmut Y. Celiker

Roswell Park Cancer Institute; Recruiting

Buffalo, New York, United States, 14263

Contact: Site Public Contact 800-767-9355 askroswell@roswellpark.org

Principal Investigator: Clare J. Twist

NYU Winthrop Hospital; Recruiting

Mineola, New York, United States, 11501

Contact: Site Public Contact CancerTrials@nyulangone.org

Principal Investigator: Chana L. Glasser

The Steven and Alexandra Cohen Children's Medical Center of New York; Recruiting

New Hyde Park, New York, United States, 11040

Contact: Site Public Contact 718-470-3460

Principal Investigator: Arlene S. Redner

Laura and Isaac Perlmutter Cancer Center at NYU Langone; Recruiting

New York, New York, United States, 10016

Contact: Site Public Contact CancerTrials@nyulangone.org

Principal Investigator: Sharon L. Gardner

Mount Sinai Hospital; Recruiting

New York, New York, United States, 10029

Contact: Site Public Contact 212-824-7309 CCTO@mssm.edu

Principal Investigator: Gary D. Crouch

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center; Recruiting

New York, New York, United States, 10032

Contact: Site Public Contact 212-305-6361 nr2616@cumc.columbia.edu

Principal Investigator: Justine M. Kahn

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Site Public Contact 212-639-7592

Principal Investigator: Neerav N. Shukla

NYP/Weill Cornell Medical Center; Recruiting

New York, New York, United States, 10065

Contact: Site Public Contact 212-746-1848

Principal Investigator: Alexander J. Chou

University of Rochester; Recruiting

Rochester, New York, United States, 14642

Contact: Site Public Contact 585-275-5830

Principal Investigator: Craig A. Mullen

Stony Brook University Medical Center; Recruiting

Stony Brook, New York, United States, 11794

Contact: Site Public Contact 800-862-2215

Principal Investigator: Laura E. Hogan

State University of New York Upstate Medical University; Recruiting

Syracuse, New York, United States, 13210

Contact: Site Public Contact 315-464-5476

Principal Investigator: Philip M. Monteleone

New York Medical College; Recruiting

Valhalla, New York, United States, 10595

Contact: Site Public Contact 914-594-3794

Principal Investigator: Jessica C. Hochberg

United States, North Carolina

Mission Hospital; Recruiting

Asheville, North Carolina, United States, 28801

Contact: Site Public Contact 828-213-7055 NCDV.ResearchRegulatory@HCAHealthcare.com

Principal Investigator: Douglas J. Scothorn

UNC Lineberger Comprehensive Cancer Center; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Site Public Contact 877-668-0683 cancerclinicaltrials@med.unc.edu

Principal Investigator: Stuart H. Gold

Carolinas Medical Center/Levine Cancer Institute; Recruiting

Charlotte, North Carolina, United States, 28203

Contact: Site Public Contact 800-804-9376

Principal Investigator: Joel A. Kaplan

Novant Health Presbyterian Medical Center; Recruiting

Charlotte, North Carolina, United States, 28204

Contact: Site Public Contact 980-201-6360 kashah@novanthealth.org

Principal Investigator: Jessica A. Bell

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Site Public Contact 888-275-3853

Principal Investigator: Lars M. Wagner

East Carolina University; Recruiting

Greenville, North Carolina, United States, 27834

Contact: Site Public Contact 252-744-1015 eubankss@ecu.edu

Principal Investigator: Andrea R. Whitfield

Wake Forest University Health Sciences; Recruiting

Winston-Salem, North Carolina, United States, 27157

Contact: Site Public Contact 336-713-6771

Principal Investigator: David E. Kram

United States, North Dakota

Sanford Broadway Medical Center; Recruiting

Fargo, North Dakota, United States, 58122

Contact: Site Public Contact 701-323-5760 OncologyClinicalTrialsFargo@sanfordhealth.org

Principal Investigator: Samuel J. Milanovich

United States, Ohio

Children's Hospital Medical Center of Akron; Recruiting

Akron, Ohio, United States, 44308

Contact: Site Public Contact 330-543-3193

Principal Investigator: Steven J. Kuerbitz

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229

Contact: Site Public Contact 513-636-2799 cancer@cchmc.org

Principal Investigator: Lauren Pommert

Rainbow Babies and Childrens Hospital; Recruiting

Cleveland, Ohio, United States, 44106

Contact: Site Public Contact 216-844-5437

Principal Investigator: Duncan S. Stearns

Cleveland Clinic Foundation; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Site Public Contact 866-223-8100 TaussigResearch@ccf.org

Principal Investigator: Rabi Hanna

Nationwide Children's Hospital; Recruiting

Columbus, Ohio, United States, 43205

Contact: Site Public Contact 614-072-2657 amy.yekisa@nationwidechildrens.org

Principal Investigator: Mark A. Ranalli

Dayton Children's Hospital; Recruiting

Dayton, Ohio, United States, 45404

Contact: Site Public Contact 800-228-4055

Principal Investigator: Mukund G. Dole

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital; Recruiting

Toledo, Ohio, United States, 43606

Contact: Site Public Contact 419-824-1842

Principal Investigator: Jamie L. Dargart

United States, Oklahoma

University of Oklahoma Health Sciences Center; Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contact: Site Public Contact 405-271-8777 ou-clinical-trials@ouhsc.edu

Principal Investigator: Rene Y. McNall-Knapp

United States, Oregon

Legacy Emanuel Children's Hospital; Recruiting

Portland, Oregon, United States, 97227

Contact: Site Public Contact 503-413-2560

Principal Investigator: Janice F. Olson

Oregon Health and Science University; Recruiting

Portland, Oregon, United States, 97239

Contact: Site Public Contact 503-494-1080 trials@ohsu.edu

Principal Investigator: Bill H. Chang

United States, Pennsylvania

Lehigh Valley Hospital-Cedar Crest; Recruiting

Allentown, Pennsylvania, United States, 18103

Contact: Site Public Contact 610-402-9543 Morgan_M.Horton@lvhn.org

Principal Investigator: Jacob A. Troutman

Geisinger Medical Center; Recruiting

Danville, Pennsylvania, United States, 17822

Contact: Site Public Contact 570-271-5251 HemonCCTrials@geisinger.edu

Principal Investigator: Jagadeesh Ramdas

Penn State Children's Hospital; Recruiting

Hershey, Pennsylvania, United States, 17033

Contact: Site Public Contact 717-531-6012

Principal Investigator: Lisa M. McGregor

Children's Hospital of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Site Public Contact 267-425-5544 CancerTrials@email.chop.edu

Principal Investigator: Richard Aplenc

Saint Christopher's Hospital for Children; Recruiting

Philadelphia, Pennsylvania, United States, 19134

Contact: Site Public Contact 215-427-8991

Principal Investigator: Gregory E. Halligan

Children's Hospital of Pittsburgh of UPMC; Recruiting

Pittsburgh, Pennsylvania, United States, 15224

Contact: Site Public Contact 412-692-8570 jean.tersak@chp.edu

Principal Investigator: Jean M. Tersak

United States, Rhode Island

Rhode Island Hospital; Recruiting

Providence, Rhode Island, United States, 02903

Contact: Site Public Contact 401-444-1488

Principal Investigator: Jennifer J. Welch

United States, South Carolina

Medical University of South Carolina; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Site Public Contact 843-792-9321 hcc-clinical-trials@musc.edu

Principal Investigator: Jacqueline M. Kraveka

Prisma Health Richland Hospital; Recruiting

Columbia, South Carolina, United States, 29203

Contact: Site Public Contact 864-241-6251

Principal Investigator: Stuart L. Cramer

BI-LO Charities Children's Cancer Center; Recruiting

Greenville, South Carolina, United States, 29605

Contact: Site Public Contact 864-241-6251

Principal Investigator: Aniket Saha

United States, South Dakota

Sanford USD Medical Center - Sioux Falls; Recruiting

Sioux Falls, South Dakota, United States, 57117-5134

Contact: Site Public Contact 605-312-3320 OncologyClinicalTrialsSF@SanfordHealth.org

Principal Investigator: Kayelyn J. Wagner

United States, Tennessee

T C Thompson Children's Hospital; Recruiting

Chattanooga, Tennessee, United States, 37403

Contact: Site Public Contact 865-331-1812

Principal Investigator: Meghann P. McManus

East Tennessee Childrens Hospital; Recruiting

Knoxville, Tennessee, United States, 37916

Contact: Site Public Contact 865-541-8266

Principal Investigator: Susan E. Spiller

The Children's Hospital at TriStar Centennial; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Site Public Contact 615-342-1919

Principal Investigator: Jennifer A. Domm

Vanderbilt University/Ingram Cancer Center; Recruiting

Nashville, Tennessee, United States, 37232

Contact: Site Public Contact 800-811-8480

Principal Investigator: Sara Zarnegar-Lumley

United States, Texas

Dell Children's Medical Center of Central Texas; Recruiting

Austin, Texas, United States, 78723

Contact: Site Public Contact 512-628-1902 TXAUS-DL-SFCHemonc.research@ascension.org

Principal Investigator: Shannon M. Cohn

Driscoll Children's Hospital; Recruiting

Corpus Christi, Texas, United States, 78411

Contact: Site Public Contact 361-694-5311 Crystal.DeLosSantos@dchstx.org

Principal Investigator: Nkechi I. Mba

Medical City Dallas Hospital; Recruiting

Dallas, Texas, United States, 75230

Contact: Site Public Contact 972-566-5588

Principal Investigator: Stanton C. Goldman

UT Southwestern/Simmons Cancer Center-Dallas; Recruiting

Dallas, Texas, United States, 75390

Contact: Site Public Contact 214-648-7097 canceranswerline@UTSouthwestern.edu

Principal Investigator: Tamra L. Slone

El Paso Children's Hospital; Recruiting

El Paso, Texas, United States, 79905

Contact: Site Public Contact 915-298-5444 ranjan.bista@ttuhsc.edu

Principal Investigator: Ranjan Bista

Cook Children's Medical Center; Recruiting

Fort Worth, Texas, United States, 76104

Contact: Site Public Contact 682-885-2103 CookChildrensResearch@cookchildrens.org

Principal Investigator: Kenneth M. Heym

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Site Public Contact 713-798-1354 burton@bcm.edu

Principal Investigator: Alexandra M. Stevens

M D Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Site Public Contact 877-632-6789 askmdanderson@mdanderson.org

Principal Investigator: Najat C. Daw

Children's Hospital of San Antonio; Recruiting

San Antonio, Texas, United States, 78207

Contact: Site Public Contact helpdesk@childrensoncologygroup.org

Principal Investigator: Timothy C. Griffin

Methodist Children's Hospital of South Texas; Recruiting

San Antonio, Texas, United States, 78229

Contact: Site Public Contact 210-575-6240 Vinod.GidvaniDiaz@hcahealthcare.com

Principal Investigator: Jose M. Esquilin

University of Texas Health Science Center at San Antonio; Recruiting

San Antonio, Texas, United States, 78229

Contact: Site Public Contact 210-450-3800 phoresearchoffice@uthscsa.edu

Principal Investigator: Anne-Marie R. Langevin

Scott and White Memorial Hospital; Recruiting

Temple, Texas, United States, 76508

Contact: Site Public Contact 254-724-5407

Principal Investigator: Nicholas W. McGregor

United States, Utah

Primary Children's Hospital; Recruiting

Salt Lake City, Utah, United States, 84113

Contact: Site Public Contact 801-585-5270

Principal Investigator: Mallorie B. Heneghan

United States, Vermont

University of Vermont and State Agricultural College; Recruiting

Burlington, Vermont, United States, 05405

Contact: Site Public Contact 802-656-8990 rpo@uvm.edu

Principal Investigator: Jessica L. Heath

United States, Virginia

Inova Fairfax Hospital; Recruiting

Falls Church, Virginia, United States, 22042

Contact: Site Public Contact 703-208-6650 Stephanie.VanBebber@inova.org

Principal Investigator: Robin Y. Dulman

Children's Hospital of The King's Daughters; Recruiting

Norfolk, Virginia, United States, 23507

Contact: Site Public Contact 757-668-7243 CCBDCresearch@chkd.org

Principal Investigator: Eric J. Lowe

Naval Medical Center - Portsmouth; Recruiting

Portsmouth, Virginia, United States, 23708-2197

Contact: Site Public Contact 757-953-5939

Principal Investigator: Bethany M. Mikles

Virginia Commonwealth University/Massey Cancer Center; Recruiting

Richmond, Virginia, United States, 23298

Contact: Site Public Contact CTOclinops@vcu.edu

Principal Investigator: Jordyn R. Griffin

Carilion Children's; Recruiting

Roanoke, Virginia, United States, 24014

Contact: Site Public Contact 540-266-6238 wpmccarty@carilionclinic.org

Principal Investigator: Erwood G. Edwards

United States, Washington

Seattle Children's Hospital; Recruiting

Seattle, Washington, United States, 98105

Contact: Site Public Contact 866-987-2000

Principal Investigator: Sarah E. Leary

Providence Sacred Heart Medical Center and Children's Hospital; Recruiting

Spokane, Washington, United States, 99204

Contact: Site Public Contact 800-228-6618 HopeBeginsHere@providence.org

Principal Investigator: Judy L. Felgenhauer

Mary Bridge Children's Hospital and Health Center; Recruiting

Tacoma, Washington, United States, 98405

Contact: Site Public Contact 253-403-1461 research@multicare.org

Principal Investigator: Robert G. Irwin

Madigan Army Medical Center; Recruiting

Tacoma, Washington, United States, 98431

Contact: Site Public Contact 253-968-6144 Melissa.a.forouhar.mil@mail.mil

Principal Investigator: Melissa A. Forouhar

United States, West Virginia

West Virginia University Charleston Division; Recruiting

Charleston, West Virginia, United States, 25304

Contact: Site Public Contact 304-388-9944

Principal Investigator: Mohamad H. Badawi

United States, Wisconsin

Saint Vincent Hospital Cancer Center Green Bay; Recruiting

Green Bay, Wisconsin, United States, 54301

Contact: Site Public Contact 920-433-8889 ewd_research_admin@hshs.org

Principal Investigator: Catherine A. Long

University of Wisconsin Carbone Cancer Center; Recruiting

Madison, Wisconsin, United States, 53792

Contact: Site Public Contact 800-622-8922

Principal Investigator: Kenneth B. De Santes

Marshfield Medical Center-Marshfield; Recruiting

Marshfield, Wisconsin, United States, 54449

Contact: Site Public Contact 800-782-8581 oncology.clinical.trials@marshfieldresearch.org

Principal Investigator: Michelle A. Manalang

Children's Hospital of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Site Public Contact 414-955-4727 MACCCTO@mcw.edu

Principal Investigator: Michael J. Burke

Canada, Alberta

University of Alberta Hospital; Recruiting

Edmonton, Alberta, Canada, T6G 2B7

Contact: Site Public Contact 780-407-6615 val.taylor@albertahealthservices.ca

Principal Investigator: Sarah J. McKillop

Canada, Manitoba

CancerCare Manitoba; Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Contact: Site Public Contact 866-561-1026 ctu_web@cancercare.mb.ca

Principal Investigator: Ashley Chopek

Canada, Nova Scotia

IWK Health Centre; Recruiting

Halifax, Nova Scotia, Canada, B3K 6R8

Contact: Site Public Contact 902-470-8037 Research@iwk.nshealth.ca

Principal Investigator: Craig Erker

Canada, Ontario

McMaster Children's Hospital at Hamilton Health Sciences; Recruiting

Hamilton, Ontario, Canada, L8N 3Z5

Contact: Site Public Contact 905-521-2100

Principal Investigator: Uma H. Athale

Children's Hospital; Recruiting

London, Ontario, Canada, N6A 5W9

Contact: Site Public Contact 519-685-8306

Principal Investigator: Shayna M. Zelcer

Children's Hospital of Eastern Ontario; Recruiting

Ottawa, Ontario, Canada, K1H 8L1

Contact: Site Public Contact 613-738-3931

Principal Investigator: Donna L. Johnston

Hospital for Sick Children; Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contact: Site Public Contact 416-813-7654 ask.CRS@sickkids.ca

Principal Investigator: Johann Hitzler

Canada, Quebec

The Montreal Children's Hospital of the MUHC; Recruiting

Montreal, Quebec, Canada, H3H 1P3

Contact: Site Public Contact 514-412-4445 info@thechildren.com

Principal Investigator: Sharon B. Abish

Centre Hospitalier Universitaire Sainte-Justine; Recruiting

Montreal, Quebec, Canada, H3T 1C5

Contact: Site Public Contact 514-345-4931 yvan.samson@umontreal.ca

Principal Investigator: Yvan Samson

Canada

Centre Hospitalier Universitaire de Quebec; Recruiting

Quebec, Canada, G1V 4G2

Contact: Site Public Contact 418-525-4444

Principal Investigator: Bruno Michon

Puerto Rico

University Pediatric Hospital; Recruiting

San Juan, Puerto Rico, 00926

Contact: Site Public Contact 787-474-0333

Principal Investigator: Maria E. Echevarria

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Todd M Cooper; Children's Oncology Group

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT04293562
• Other Study ID Numbers: AAML1831; NCI-2020-00546 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); AAML1831 ( Other Identifier: Children's Oncology Group ); AAML1831 ( Other Identifier: CTEP ); U10CA180886 ( U.S. NIH Grant/Contract )
• First Posted: March 3, 2020
• Last Update Posted: May 4, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cytarabine; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Methotrexate; Etoposide; Etoposide phosphate; Daunorubicin; Asparaginase; Mitoxantrone; Podophyllotoxin; Gemtuzumab; Dexrazoxane; Razoxane; Calicheamicins; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents