Leukemia Clinical Trials

• STEP 0: Patient must be ≤ 21 years of age

‣ PLEASE NOTE: Eligibility criteria to enroll onto Step 1 for the treatment trial is ≤ 21 years of age at the time of Step 1 enrollment. Please plan accordingly to ensure that patients who are screened with Step 0 will be at an eligible age at the time of enrollment onto Step 1. Patients who are 21 at the time of screening who turn 22 at the time of enrollment onto Step 1 will not be eligible to enroll onto the study

• STEP 0: Patients with newly diagnosed high risk\* de novo AML, newly diagnosed therapy-related AML, relapsed, or refractory AML. in complete remission at the time of transplant. Patients with a history of isolated or combined central nervous system (CNS) or extramedullary disease are eligible if they have no evidence of active CNS or extramedullary disease at the time of trial enrollment (Step 0) and treatment enrollment (Step 1). Eligible patients with histories of isolated or combined CNS or extramedullary disease at time of relapse are required to be in complete remission at time of transplant to be eligible for this study

‣ Based on risk criteria adopted by the AAML1831 study

• STEP 0: Patient must plan to have bone marrow sample submitted to Hematologics within 14 days prior to the start of conditioning regimen for HCT.

‣ Note: In order to be eligible to enroll onto Step 1 to receive treatment on this study, pre-HCT disease status must be assessed prior to receiving HCT. AML must be in complete remission (Children's Oncology Group \[COG\]-complete remission \[CR\], COG-complete remission with partial recovery of platelelt count \[CRp\], COG-complete remission with incomplete blood count recovery \[Cri\], with or without detectable minimal residual disease \[MRD\]); bone marrow CR must be assessed by central flow cytometry performed at Hematologics prior to the start of the conditioning regimen

• STEP 0: Human immunodeficiency virus (HIV)-infected patients are eligible for this trial if the following criteria are met:

‣ No history of HIV complications with the exception of CD4 count \< 200cells/mm\^3

⁃ No antiretroviral therapy with overlapping toxicity such as myelosuppression

⁃ CD4 count \> 500 cells/mm\^3 prior to the diagnosis of newly diagnosed, relapsed, refractory AML.

⁃ HIV viral loads below the limit of detection within 6 months, as long as the patient is NOT receiving anti-retroviral agents that may interact with ASTX727.

⁃ No history of highly active antiretroviral therapy (HAART)-resistant HIV

• STEP 0: Patients must be receiving an allogeneic (related, unrelated, and mismatched related, including haploidentical) marrow, peripheral blood, or cord blood transplant for the first time

• STEP 0: HCT conditioning regimen must be planned to begin within 14 days after bone marrow assessment to determine disease status

• STEP 0: Conditioning regimen must be myeloablative and include high dose busulfan, or treosulfan, or total body irradiation

• STEP 0: Patients must not have received prior exposure to ASTX727. Note that patients may have had prior exposure to decitabine

• STEP 1: Patient must be ≤ 21 years of age at the time of study enrollment to step 0 and step 1

• STEP 1: Patients must have a body surface area ≥ 1m\^2 at enrollment to step 1

• STEP 1 (PRE-HCT): AML must be in complete remission (COG-CR, COG-CRp, COG-Cri), with or without detectable MRD; bone marrow CR must be assessed by central flow cytometry performed at Hematologics. Disease assessment must be performed within 14 days prior to the start of HCT conditioning regimen

‣ Patients with CNS or extramedullary disease within 14 days prior to the start of the HCT condition regimen are not eligible

• STEP 1 (POST-HCT): AML must be in complete remission (COG-CR, COG-CRp, COG-CRi). Bone marrow evaluation must show CR with no detectable minimal residual disease (MRD negative by central flow cytometry at Hematologics)

‣ Note: Disease assessment is required to be performed within 14 days prior to enrollment onto Step 1

⁃ Patients with CNS or extramedullary disease post-HCT are not eligible

• STEP 1: Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age. Patients must have Karnofsky performance score ≥ 50 or Lansky play-performance scale score ≥ 50

• STEP 1: Patients must have fully recovered from the acute toxicities related to the conditioning regimen and the transplant. If, after 42-100 days post-transplant, the eligibility criteria are met, the patient is considered to have recovered adequately

• STEP 1: Platelet count ≥ 50,000 µL (without requirement for platelet transfusion within the last 7 days)

• STEP 1: Hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions)

• STEP 1: Absolute neutrophil count ≥ 1,000 µL with no myeloid growth factor support within the last 3 days

• Estimated glomerular filtration rate (GFR) (eGFR) ≥ 60 mL/min/1.73 m\^2 Bedside Schwartz formula (2009) OR

‣ OR- A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2

⁃ A GFR ≥ 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)

⁃ Note: Estimated GFR (eGFR) from cystatin C or other estimates not listed above are not acceptable for determining eligibility

• STEP 1: Bilirubin (total or sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age

• STEP 1: Alanine aminotransferase (ALT) ≤ 3 x ULN

• STEP 1: Aspartate aminotransferase (AST) ≤ 3 x ULN

• STEP 1: Albumin ≥ 2 g/dL