Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL

Inclusion Criteria

• Inclusion Criteria: - Age ≥ 18 years. - All subjects must have histologically or pathologically confirmed diagnosis of their malignancy and/ or measurable R/ R disease, as follows: 1. Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood. 2. Cohort 2 only: Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously indolent lymphoma (e.g., follicular lymphoma) with documented clinical or radiological evidence of progressive or persistent disease. At study entry, subjects must have measurable disease as per the revised criteria for response assessment of lymphoma. 3. Cohort 3 only: Measurable MM. 4. Cohort 4 only: Previously treated subjects with active CLL/SLL with meeting at least 1 of the iwCLL 2018 criteria for requiring treatment. - Subjects must be refractory or must have progressed on, or following discontinuation of the most recent anti-cancer therapy, with the following considerations: 1. Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation). 2. Cohort 2 only: Must have received at least 2 previous systemic regimens for the treatment of their de novo or transformed DLBCL. 3. Cohort 3 only: Must have received at least 3 anti-MM regimens including proteasome inhibitor. 4. Cohort 4 only: Must have received at least 2 prior systemic treatment regimens. - ECOG performance status of 0-2 and an estimated expected life expectancy of > 3 months in the opinion of the Investigator. - Adequate organ function. - Both men and women of childbearing potential or their partners must use adequate birth control measures during the course of the trial and for at least 90 days after discontinuing study treatment. Exclusion Criteria: Subjects who meet any of the following criteria will not be enrolled in the study (all cohorts, unless otherwise indicated): - Certain disease subtypes or occurrences, as follows: 1. Cohort 1: Acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis. 2. Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL). 3. Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis. 4. Cohort 4: Known or suspected history of Richter's transformation. - White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy) (Cohort 1 only). - Known central nervous involvement, as follows: 1. Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable. 2. Cohort 2: Active CNS lymphoma or meningeal involvement. 3. Cohort 3: Active CNS MM. 4. Cohort 4: Active CNS leukemia. - Prior menin inhibitor therapy. - Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen. - Subjects with a pre-existing disorder predisposing them to a serious or life-threatening infection. - An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.