A Study of Revumenib and Mezigdomide in People With Leukemia

The purpose of this study is to find out whether the combination of mezigdomide and revumenib is a safe treatment for people with relapsed or refractory KMT2A-r, NUP98-r, and NPM1-m acute leukemias.

Inclusion Criteria: * Participant must be ≥ 12 years of age at the time of signing the informed consent form (ICF). * Participant must weigh at least 40 kg * Participant is willing and able to adhere to the study visit schedule and other protocol requirements. * Participant has relapsed/refractory acute leukemia defined acute myeloid leukemia, acute lymphoblastic leukemia, or mixed phenotype acute leukemia after as failure of at least 1 prior line of therapy (can be either primary refractory disease or progression during or after treatment) * Participant has confirmed acute leukemia with detectable NPM1c, KMT2A translocation, or NUP98 translocation. 1. At MSK, NPM1 testing utilizes MSK-REACT, a rapid multi-gene NGS panel used in all new AML diagnoses that is clinically validated by the Laboratory of Diagnostic Molecular Pathology pursuant to the requirements of CLIA'88 and approved by New York State, or MSK-IMPACT, a multi-gene NGS panel, which is authorized by the FDA. At non-MSK sites, NPM1 testing may be performed in local CLIA-certified laboratories using validated clinical assays with capable of detecting NPM1c variants at a frequency of ≥5%. Eligible patients must have an NPM1c (nucleophosmin) exon 12 variant as determined by these assays. 2. At MSK, KMT2A and NUP98 testing will utilize chromosomal analysis and fluorescence in situ hybridization studies. At non-MSK sites, testing may be performed in local CLIA-certified laboratories using validated clinical assays with performance characteristics sufficient to detect relevant translocations. Eligible patients must have a KMT2A or NUP98 translocation as determined by these assays 3. The patient's chart will be utilized for screening purposes * Regarding prior treatment with a menin inhibitor: 1. Participants enrolled in Phase 1 have no requirements regarding prior treatment with a menin inhibitor 2. Participants enrolled in Phase 2, cohort 1, are required to be menin inhibitor naïve (no previous treatment with a menin inhibitor) 3. Participants enrolled in Phase 2, cohort 2, are required to be menin inhibitor exposed (previous treatment received a menin inhibitor) * Regarding prior alloSCT, at 60 days must have elapsed from day of transplant and at least 4 weeks must have elapsed from most recent donor lymphocyte infusion. * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and \