Ziftomenib for Acute Myeloid Leukemia

Key Inclusion Criteria: * Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML * Those intending treatment with intensive chemotherapy in Arm C should be NPM1-m and FLT3-ITD+ with an allelic ratio ≥0.05 and eligible for FLT3-targeted treatment * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Adequate liver, renal, and cardiac function according to protocol defined criteria * A female of childbearing potential must agree to use adequate contraception as well as a double barrier method from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or use a double barrier method of contraception from the time of screening through 180 days following the last dose of study intervention * Female patients of childbearing potential who receive quizartinib in Arm C should use a highly effective method of contraception during quizartinib treatment and for 7 months after the last dose Key Exclusion Criteria: * Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia * Known history of BCR-ABL alteration * Advanced malignant hepatic tumor * Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery * Active central nervous system (CNS) involvement by AML. * Clinical signs/symptoms of leukostasis or WBC \> 25,000 / microliter. Hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine if used per institutional SOC for control of leukocytosis are permitted to meet this criterion * Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia * Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection * For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis and/or up to 2 doses of cytarabine per institutional standards to control leukocytosis, or prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia * For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug * Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol * Mean QT interval corrected for heart rate by Fredericia's formula (QTcF) * Arm A and Arm B: \>480 ms on triplicate ECGs * Arm C: \>450 ms on triplicate ECGs * Uncontrolled infection * Women who are pregnant or lactating * An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing * Patients who have active GVHD requiring \>0.5 mg/kg prednisone or any new or increase in immunosuppressants in the prior 2 weeks for GVHD treatment