Ziftomenib + Mezigdomide in Adolesc. and Adults w/ R/R AML

Inclusion Criteria: * Age ≥16 years during dose escalation portion of study, patients must weigh ≥40 kg. * Age \>12 years during dose expansion portion of study, patients must weight ≥40 kg. * Diagnosis of AML per the WHO Classification of Hematolymphoid Tumors (5th Edition) with documented KMT2A rearrangement or NPM1 cytoplasmic-type (NPM1c) mutation. KMT2A-rearrangements must be confirmed by FISH or RNA-based fusion calling by a CLIA-certified laboratory. This study will only enroll KMT2A gene rearrangements in which there is a translocation between the N-terminal portion of KMT2A and a fusion partner, and will not include KMT2A partial tandem duplications (PTDs) or other structural alterations of KMT2A. NPM1c mutations must be confirmed by DNA sequencing in a CLIA-certified laboratory. Patients with myeloid sarcoma are eligible only if concurrent bone marrow involvement is present. Patients must have at least 5% bone marrow disease by morphology at the time of study entry. * Patients with NPM1 mutated AML must either be FLT3 ITD wild type or have an ITD allelic ratio of \<0.05 (i.e. not eligible for a targeted FLT3 tyrosine kinase inhibitor). * Patients must have relapsed or be refractory to at least one prior line of conventional therapy for AML or MDS-AML. * Eastern Cooperative Oncology Group (ECOG) performance status must be 0, 1, or 2; Karnofsky ≥50 for patients ≥16 years of age; and Lansky ≥50 for patients ≥12 to 16 years of age. * Participants must meet the followin…