Revumenib, Azacitidine, and VENetoclax in Newly Diagnosed KMT2A-Rearranged AML

This study is testing a new treatment combination called RAVEN, which includes revumenib, azacitidine, and venetoclax, in patients who are newly diagnosed with a specific type of acute myeloid leukemia (AML) called KMT2A- translocated AML. People with this type of AML often have poor outcomes, so new treatments are needed that may work better and cause fewer side effects. The study has two parts: 1. Induction Phase: Patients will receive treatment for up to 3 cycles. Each cycle lasts 28 days. The goal is to help the leukemia go into remission. 2. Continuation Phase: After remission and blood count recovery, patients will continue treatment until the leukemia returns, side effects become too severe, the patient receives a stem cell transplant, or another reason to stop treatment occurs. Patients who receive an allogeneic stem cell transplant (stem cells from a donor) may also join a separate part of the study to test revumenib as maintenance treatment after transplant.

Inclusion Criteria: * Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. * Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee. * Age 18-65 years at the time of consent. * Untreated AML based on 2022 WHO or ICC criteria with KMT2A translocation by local standard diagnostic testing by cytogenetics/karyotype or FISH Exclusion Criteria: * Isolated myeloid sarcoma (patients must have blood or marrow involvement with AML to enter study) * Active central nervous system (CNS) involvement by AML. Of note, patients are eligible if CNS leukemia is in remission at the time of study entry. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).