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

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. B. Adult male or female patients 18 years of age or older. C. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 (Appendix A: Performance Status Scales). D. Patients must satisfy the following laboratory criteria:

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. H. Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia. I. Uncontrolled human immunodeficiency virus (HIV), defined as dateable viral load. J. Known hepatitis B surface antigen seropositive. (Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load if they are to participate in this study.) K. Known active hepatitis C infections. (Note: Patients who are hepatitis C surface antigen-positive are eligible if they have an undetectable hepatitis C viral load.) L. Females of child-bearing potential who refuse to either practice 2 effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 30 days after the last dose of study drug. M. Sexually active males who refuse to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (includes males surgically sterilized - i.e., status post vasectomy). N. Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug. O. Female patients who intend to donate eggs (ova) during the course of this study or within 4 months after receiving their last dose of study drug. P. Male patients who intend to donate sperm during the course of this study or within 4 months after receiving their last dose of study drug. Q. Any serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of study procedures. R. Symptomatic central nervous system (CNS) involvement. S. Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection. T. Known hepatic cirrhosis or severe pre-existing hepatic impairment. U. Current use of a prohibited medication (Section 4.12) or expected to require any of these medications during treatment with study drug. V. Patients with uncontrolled coagulopathy or bleeding disorder. W. Life-threatening illness unrelated to cancer. X. Patients with impaired decision-making capacity.