A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia

Inclusion Criteria:

* 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)

Exclusion Criteria:

* STEP 0 PRE-TRANSPLANT EXCLUSION CRITERIA:
* Participants who have had a previous hematopoietic stem cell transplantation
* Participants who previously experienced a serious toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] grade 4) attributed to revumenib (probably or definitely related)
* Participants who previously experienced a relapse while receiving revumenib
* Patients diagnosed with Down syndrome
* Patients known to have one of the following syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman syndrome, or any other known bone marrow failure syndrome
* Patients with a secondary KMT2A-r leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy
* Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrythmia in the past 6 months prior to study enrollment
* AML with FLT3 ITD or other activating mutation, unless disease has proven unresponsive to TKI therapy or patient has experienced serious TKI related toxicity
* Estimated glomerular filtration rate (GFR) of \< 60 mL/min/1.73 m\^2
* Cardiac ejection fraction \< 50% or shortening fraction \< 27% (ECHO may be performed 3 months prior)
* Clinical evidence of pulmonary disease or need for continuous supplemental oxygen for greater than 24 hours
* Uncontrolled infection
* Patients who have received another investigational drug within 30 days prior to Step 0 enrollment
* STEP 1 EXCLUSION CRITERIA:
* Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study and for 4 months after the last revumenib dose. Abstinence is an acceptable method of birth control
* Patients who are currently receiving another investigational drug are not eligible.
* Patients who are currently receiving other anti-cancer agents are not eligible. Patients receiving intrathecal chemotherapy in the prior 14 days are eligible
* Moderate or strong CYP3A4 inducers are prohibited during treatment. These agents should be discontinued at least 7 days prior to starting protocol therapy. Concomitant use of strong CYP3A4 inhibitors is permitted with appropriate revumenib dose modification
* Avoid concomitant use with other drugs with a known potential to prolong QTc interval
* Patient is not able to start the first cycle of revumenib from day +42 through day +100 post-HSCT
* Patients with graft loss are not eligible
* Patients with steroid refractory or dependent acute grade 3-4 graft versus host disease (GVHD) are not eligible
* Patients who have an uncontrolled viral, bacterial, fungal, or protozoal infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible