Revumenib is a first in class oral menin inhibitor that targets a central oncogenic dependency shared across KMT2Ar, NPM1m, and NUP98r AML. In addition to suppressing leukemogenic transcriptional programs and promoting leukemic differentiation, menin inhibition has been shown to modulate epigenetic states linked to antigen presentation and immune recognition. These properties provide a strong biological rationale for evaluating revumenib as maintenance therapy following alloHCT, with the goal of suppressing residual leukemic clones while preserving or enhancing GVL activity during immune reconstitution.

Menin is a critical cofactor for oncogenic transcriptional programs in AML subsets driven by KMT2A rearrangements, NPM1 mutations, and NUP98 rearrangements. The interaction between menin and KMT2A promotes aberrant expression of HOX and MEIS genes, maintaining leukemic self-renewal and blocking differentiation. Revumenib is a potent, selective, oral small-molecule inhibitor of the menin-KMT2A interaction that has demonstrated clinical activity in relapsed or refractory AML. Beyond its direct anti-leukemic effects, emerging preclinical data indicate that menin inhibition may favorably modulate leukemia-immune interactions in the post-transplant environment. Menin inhibition has been shown to induce myeloid differentiation and increase expression of antigen presentation machinery, including MHC class II, in KMT2Ar and NPM1m AML. This effect is mediated through activation of interferon-related signaling pathways and results in enhanced recognition of leukemia cells by donor T cells. In parallel, menin inhibition has been shown to augment donor T-cell effector function and reduce T-cell exhaustion, collectively strengthening the GVL response without directly increasing alloreactivity against normal tissues.

Inclusion Criteria:

Inclusion Criteria:

1. Aged ≥18 years at the time of signing informed consent
2. Able to provide written informed consent personally or via a legally authorized representative in accordance with applicable regulatory and institutional requirements
3. Willing and able to comply with all study procedures and available for the duration of the study
4. Diagnosis of acute myeloid leukemia (AML) in complete morphologic remission with one of the following molecular abnormalities:

1. KMT2A-rearranged (KMT2Ar) AML (Excluding KMT2A partial tandem duplication (KMT2A-PTD) 2. NPM1-mutated (NPM1m) AML (Including FLT3-ITD or TKD co-mutation) 3. NUP98-rearranged (NUP98r) AML 5. Planned first allogeneic hematopoietic cell transplantation (allo-HCT) for AML.

6. Transplant Characteristics

1. Planned allo-HCT using bone marrow or peripheral blood stem cell graft source.
2. Planned reduced-intensity/non-myeloablative conditioning (RIC/NMA) or myeloablative conditioning (MAC), using a conditioning regimen permitted- by the protocol and consistent with standard clinical practice, meeting CIBMTR criteria for conditioning intensity

7. Planned donor:

1. HLA-matched related donor (5/6 or 6/6)
2. Matched unrelated donor (8/8)
3. Mismatched unrelated donor (7/8)
4. Haploidentical donor meeting institutional requirements

8. Performance Status:

1. Karnofsky Performance Status ≥70%. 9. Cardiac Function: left ventricular ejection fraction (LVEF) by transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) with no clinical evidence of heart failure: RIC/NMA: ≥50% MAC: ≥5 10. Pulmonary function meeting the following criteria, without supplemental oxygen other than CPAP:

1. RIC/NMA: DLCO (corrected for hemoglobin) and FEV1 ≥40% predicted
2. MAC: DLCO and FEV1 ≥50% predicted

11. Renal Function: estimated creatinine clearance (CrCl) ≥45mL/min calculated using the Cockcroft-Gault formula or 24-hour urine collection, consistent with standard eligibility criteria for allogeneic HCT recipients.

12. Liver function acceptable per local institutional guidelines for allo-HCT eligibility.

13. Reproductive Status: Willingness to use contraception in accordance with local regulations from first study intervention through the required contraceptive period Willingness to use contraception in accordance with local regulations from first study intervention through the required contraceptive period

Exclusion Criteria:

1. Disease Status:

   a. Evidence of active AML prior to HCT, assessed within 42 days before transplant, defined as any of the following:

   • ≥5% bone marrow blasts
   • Circulating blasts within 14 days before conditioning
   • CNS or other extramedullary disease

2. Other active malignancy that, in the investigator's judgment, could interfere with safety or efficacy assessment

3. Treatment with non-protocol antileukemic therapy (donor lymphocyte infusion for relapse prophylaxis or treatment will be considered an EFS event)

4. Cardiac / QT Risk

   1. Requirement for concomitant medications known to prolong QT/QTc interval, except low-risk agents used as standard supportive care
   2. Diagnosis or suspicion of Long QT syndrome, or a family history of Long QT syndrome
   3. Fridericia's corrected QT interval (QTcF) >450 msec.
   4. History within 6 months of study entry of:

   i. Myocardial infarction ii. Unstable angina iii. Congestive heart failure (NYHA Class ≥ II) iv. Life-threatening or uncontrolled arrhythmia v. Cerebrovascular accident or transient ischemic attack

5. Chronic respiratory disease requiring continuous supplemental oxygen, or other significant organ dysfunction that would adversely affect study participation.

6. Active, uncontrolled infection, including any of the following:

   1. Active, uncontrolled systemic fungal, bacterial, or viral infection within 14 days prior to the start of conditioning
   2. Any other documented active, uncontrolled infection at the start of conditioning

7. Chronic viral infections with evidence of active disease, including:

   HIV: detectable viral load within 6 months prior to screening

   Hepatitis B:

   • HBsAg-positive and/or anti-HBc-positive with detectable HBV DNA
   • Anti-HBc-positive alone Hepatitis C: positive HCV antibody with detectable HCV RNA

8. Planned HCT using cord blood, ex vivo T cell depletion, engineered grafts, or experimental graft sources

9. Malabsorption syndrome or GI condition that precludes oral administration, including:

   1. Inability to swallow oral medications
   2. Prior gastric bypass or severe gastroparesis
   3. Cirrhosis with Child-Pugh Class B or C

10. Pregnant or breastfeeding

11. Prior intolerance to menin inhibitor therapy resulting in ≥ Grade 3 treatment-related adverse events

12. Any condition, therapy, laboratory abnormality, or allergy to excipients that, in the investigator's judgment, could confound study results, interfere with the participant's ability to comply with study procedures or complete the study, or make participation not in the participant's best interest.