Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant

Inclusion Criteria

• PARTICIPANTS WHO ARE SCHEDULED TO UNDERGO HEMATOPOIETIC CELL TRANSPLANTATION (HCT) (PRE-SCREENING): Documented informed consent of the participant and/or legally authorized representative
• PARTICIPANTS WHO ARE SCHEDULED TO UNDERGO HCT (PRE-SCREENING): Agreement to allow the use of archival tissue from diagnostic tumor biopsies; if unavailable, exceptions may be granted with study principal investigator (PI) approval
• PARTICIPANTS WHO ARE SCHEDULED TO UNDERGO HCT (PRE-SCREENING): Age: >= 2 years
• PARTICIPANTS WHO ARE SCHEDULED TO UNDERGO HCT (PRE-SCREENING): Have a date for transplant scheduled within the next 30 days or have received transplant within the last 30 days. * Note: all transplant donors, conditioning regimens and GVHD prophylaxis regimens will be acceptable
• PARTICIPANTS WHO ARE SCHEDULED TO UNDERGO HCT (PRE-SCREENING): Participant was diagnosed with an acute leukemia as defined by the World Health Organization (WHO) 5th edition criteria for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or acute leukemia with ambiguous lineage that is in morphologic remission (< 5% blasts in bone marrow with no extramedullary disease, MRD+ ok). Acute promyelocytic leukemia is not included
• PARTICIPANTS WHO ARE SCHEDULED TO UNDERGO HCT (PRE-SCREENING): Participant must meet one of the following disease characteristics: * Confirmed NPM1c mutant AML with at least one of the following additional characteristics ** FLT3-ITD co-mutation ** Pre-transplant MRD+ disease by flow cytometry or real time polymerase chain reaction (qPCR) ** Requires more than one AML induction regimen to acquire CR1 ** In second or later complete remission * Confirmed acute leukemia with KMT2Ar translocation by fluorescence in situ hybridization (11q23 MLL-break apart fluorescence in situ hybridization [FISH]) or next-generation sequencing (NGS). Patients with KMT2A point mutations or partial tandem duplications are not eligible
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Documented informed consent of the participant and/or legally authorized representative. * Assent, when appropriate, will be obtained per institutional guidelines
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Age: >= 2 years
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky Performance Status (KPS) >= 70, or Lansky Score of >= 70 if aged < 18 years
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Participant must have confirmed one of the following (NPM1c or KMT2Ar) during pre-screening: * NPM1c mutant AML with at least one of the following additional characteristics ** FLT3-ITD co-mutation ** Pre-transplant MRD+ disease by flow cytometry or qPCR ** Requires more than one AML induction regimen to acquire CR1 ** In second or later complete remission * Acute leukemia with KMT2Ar translocation by fluorescence in situ hybridization (11q23 MLL-Break Apart FISH) or next-generation sequencing (NGS). Patients with KMT2A point mutations or partial tandem duplications are not eligible
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Participant is between day +30 and +120 after alloHCT with no morphologic evidence of relapse post-HCT
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Full engraftment post-HCT: Absolute neutrophil count (ANC) >= 500/mm^3 for 3 days * NOTE: Patients may NOT be given granulocyte colony-stimulating factor (GCSF) to meet eligibility criteria; however, they may receive GCSF after start of treatment
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Platelets >= 75,000/mm^3 * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Hemoglobin >= 9g/dL * NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert’s disease)
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Aspartate aminotransferase (AST) =< 2.5 x ULN
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Alanine aminotransferase (ALT) =< 2.5 x ULN
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Left ventricular ejection fraction (LVEF) >= 50%
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Bazett's formula-corrected QT interval (QTcB) =< 450 msec (males) or =< 470 msec (females)
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) OR * If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable. ** HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: If a female of childbearing potential, must be willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: If male of childbearing potential, must agree to use barrier contraception from the time of enrollment through 120 days following the last study drug dose * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria

• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Patients requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (e.g., diphenhydramine, famotidine, ondansetron, Bactrim, tacrolimus, azoles)
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Active grade II-IV acute GVHD, chronic GVHD (moderate or severe) and/or requiring systemic steroids with prednisone dose equivalent of >= 0.25mg/kg within 4 weeks of revumenib administration
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Female participant who is pregnant or lactating
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Participant has a malabsorption syndrome or other condition that precludes enteral route of administration
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Participant has chronic respiratory disease that requires continuous oxygen, or significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect participation in this study
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Cardiac disease: any of the following within the 6 months prior to study entry: * Myocardial infarction * Uncontrolled/unstable angina * Congestive heart failure (New York Heart Association Classification class >= II) * Life-threatening or uncontrolled arrhythmia * Cerebrovascular accident * Transient ischemic attack
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Gastrointestinal disease: * Any gastrointestinal issue of the upper gastrointestinal (GI) tract likely to affect oral drug absorption or ingestion (e.g., gastric bypass, gastroparesis, etc.) * Cirrhosis with a Child-Pugh score of B or C
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Other active malignancy; patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Treatment with any non-protocol anti-leukemic agents
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: History of or any concurrent condition, therapy, laboratory abnormality, or allergy to excipients that in the investigator’s opinion might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate
• PARTICIPANTS WHO HAVE PASSED PRE-SCREENING ELIGIBILITY: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)