Clinical Trial Radar

STEP 0 PRE-TRANSPLANT INCLUSION CRITERIA:

Patients must be ≥ 30 days and < 22 years of age

• PLEASE NOTE: Eligibility criteria to enroll onto Step 1 for the treatment trial is < 22 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

Patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or mixed phenotype acute leukemia (MPAL) with a KMT2a rearrangement, NUP98 rearrangement, or NMP1 mutation confirmed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA) certified laboratory. 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

AML and MPAL must be in morphologic complete remission confirmed by multiparameter flow (MDF) testing (with or without detectable minimal residual disease \[MRD\]). ALL must have bone marrow MRD < 0.1%

• Pre-HSCT bone marrow:

  • Assessment of disease status (complete response \[CR\] and minimal residual disease \[MRD\]) by multiparameter flow cytometry will be performed on bone marrow aspirate samples locally. Disease assessment will be required within 30 days prior to the start date of HSCT to determine CR (as part of the Step 0 screening criteria). Patients with CNS or extramedullary disease within 14 days prior to the start of the HSCT condition regimen are not eligible

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 < 200 cells/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 revumenib
• No history of highly active antiretroviral therapy (HAART)-resistant HIV

Lansky/Karnofsky performance status ≥ 70%

Must be receiving an allogeneic hematopoietic stem cell transplant (all graft and donor types will be eligible)

Must be receiving myeloablative conditioning as defined by Center for International Blood and Marrow Transplant Research (CIBMTR) criteria

STEP 1 INCLUSION CRITERIA:

Patients must be ≥ 30 days and < 22 years of age at the time of study enrollment to Step 0 and Step 1

Post-HSCT bone marrow:

• Assessment of disease status (CR and minimal residual disease \[MRD\]) by multiparameter flow cytometry will be performed on bone marrow aspirate samples locally. Disease assessment will be required within 30 days prior to enrollment onto Step 1 to confirm MRD negativity (as part of the Step 1 Enrollment eligibility criteria). Disease must be in complete remission with marrow minimal residual disease < 0.05% for AML and < 0.01% for ALL by MDF. Patients with CNS or extramedullary disease post-HSCT are not eligible

Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

Patients must have recovered from the acute pre-transplant conditioning regimen related toxicities. If, after 42-100 days post-transplant, the eligibility criteria are met in criteria below the patient is considered to have recovered adequately

• Pre-transplant exposure to revumenib will be allowed with the exception of patients who experienced a serious toxicity (CTCAE grade 4) attributed to revumenib (probably or definitely related) or those that experienced progression or relapse while receiving revumenib

For patients ≤ 17 years old estimated GFR (eGFR) ≥ 60 mL/min/1.73 m^2 "Bedside" Schwartz formula OR for any age group a 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m2 OR a GFR ≥ 60 mL/min/1.73 m2. 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) (must be performed within 7 days prior to enrollment)

For patients > 17 years old the Cockroft-Gault equation should be utilized to calculate eGFR OR for any age group a 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m2 OR a GFR ≥ 60 mL/min/1.73 m2. 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) (must be performed within 7 days prior to enrollment)

Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)

Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 3 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment)

Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment)

Albumin ≥ 2 g/dL (must be performed within 7 days prior to enrollment)

Shortening fraction of > 27% by echocardiogram, or ejection fraction of > 50% by gated radionuclide study with no evidence of congestive heart failure

Ejection fraction of > 50% by gated radionuclide study with no evidence of congestive heart failure

Corrected QT interval (QTc) < 450 ms

No evidence of pulmonary disease and without need for continuous supplemental oxygen

Potassium > 3.5mEq/L (supplementation allowed) (must be performed within 7 days prior to enrollment)

Magnesium ≥ 1.6mg/dL (supplementation allowed) (must be performed within 7 days prior to enrollment)

For patients with leukemia: platelet count ≥ 50,000 µL (without requirement for platelet transfusion within the last 7 days) (must be performed within 7 days prior to enrollment)

For patients with leukemia: hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) (must be performed within 7 days prior to enrollment)

For patients with leukemia: absolute neutrophil count ≥ 1,000 µL with no myeloid growth factor support within the last 3 days (must be performed within 7 days prior to enrollment)