A Multi-Site Break Through Cancer Trial: Phase II Study Investigating Dual Inhibition of BCL2 and Menin in AML MRD Using the Combination of Venetoclax and Revumenib

1. Prior treatment with a menin inhibitor.

2. Participants who are expected to receive standard therapy (either intensive or hypomethylating agent and venetoclax) with continued tolerability and benefit.

3. Participants who are expected to be able to proceed with stem cell transplantation within the next 30 days.

4. Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.

5. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.

6. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.

7. Participants with a concurrent active malignancy under treatment.

8. Known active hepatitis B (HBV) or Hepatitis C (HCV) or HIV infection.

9. Female subjects who are pregnant or breast-feeding.

10. Participant has an active uncontrolled infection.

11. Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.

12. QTc \>450 msec for males and QTc \>470 msec for females using the Fridericia Formula.

13. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participants's participation for the full duration of the study, or is not in the best interest of the patient to participate.

14. Clinically active central nervous system (CNS) leukemia.

15. Participants on immunosuppressive therapy post-HSCT at the time of screening (must be off all systemic immunosuppression therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks). The use of topical steroids for cutaneous graft-versus-host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted.

16. Participants with Grade \> 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.

What this study is about