Venetoclax and Bomedemstat in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Eligibility Criteria

• 1. Relapsed/refractory Acute Myeloid Leukemia (AML) following failure of at least one standard, front-line therapy. Patients must have an AML diagnosis per the World Health Organization (WHO) criteria, regardless of etiology, sub-type or treatment history.
• 1. Total bilirubin ≤ 2 upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin is ≤ 1.5 x ULN of the direct bilirubin.
• 2. Alanine aminotransferase (ALT) and aspartate transaminase (AST) must be ≤ 3 × ULN.
• 3. Calculated creatinine clearance \> 50 ml/min.
• 4. Hemoglobin \> 8 g/dL (prior red blood cell (RBC) transfusion allowed). Patients may be transfused to achieve this value. Elevated indirect bilirubin due to posttransfusion hemolysis is allowed.
• 5. White blood cell (WBC) count \< 25,000 cells/μL before administration of VenBom on Cycle 1 Day 1. Note: During Cycle 1 only, hydroxyurea may be used to control the level of circulating leukemic blast cell counts to not lower than 10,000 cells/μL.
• 6. Platelet count ≥ 20,000 cells/μL before administration of VenBom on Cycle 1 Day 1. Note: Transfusions permitted to achieve this threshold.
• 1. Are postmenopausal (No menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of menorrhoea, a single FSH measurement is insufficient.), OR
• 2. Are surgically sterile, OR
• 3. If they are of childbearing potential: Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), OR Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).
• 1. Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
• 2. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).
• 1. Uncontrolled high blood pressure (i.e., systolic blood pressure \> 180 mm Hg, diastolic blood pressure \> 95 mm Hg)
• 2. Cardiomyopathy or history of ischemic heart disease. Exception: Patients with ischemic heart disease who have received treatment for acute coronary syndrome (ACS), myocardial infarction (MI), and/or coronary artery revascularization surgery (e.g., coronary artery bypass graft, stent) greater than 6 months before screening and who are without cardiac symptoms may enroll.
• 3. Congestive heart failure (New York Heart Association (NYHA) Class III or IV or Class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 4 weeks before screening).
• 4. Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing).
• 5. Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, and pulmonary fibrosis.