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

NCT ID: NCT06284486

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-23
• Study Completion Date: 2028-12-30

Brief Summary

To learn if the combination of venetoclax and revumenib can help to control MRD-positive AML.

Detailed Description

Primary Objectives

• Phase I: To determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of revumenib and venetoclax for patients with acute myeloid leukemia (AML) and detectable minimal or measurable residual disease (MRD).
• Phase II: To assess the efficacy of the combination of venetoclax and revumenib in clearance of MRD in patients with AML.

Secondary Objectives

• To assess overall survival (OS), relapse-free survival (RFS), event-free survival (EFS) and duration of response (DOR).
• To determine clinical flow and genetic MRD concordance rate

Exploratory Objectives

• To evaluate molecular and cellular markers that may be predictive of antitumor activity and/or resistance.
• To correlate MRD negativity with clinical outcomes (survival and relapse risk)
• To evaluate concordance of standard and novel MRD assays
• To explore the safety and activity of venetoclax plus revumenib in the pediatric population

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Venetoclax + Revumenib

Participants may receive the combination of venetoclax and revumenib for up to 1 year, and then 1 more year of venetoclax alone. You will no longer be able to take the study drug(s) if the disease gets worse or if intolerable side effects occur. Participants will take venetoclax by mouth on 1 time a day at about the same time each day, on Days 1-14 of each cycle. Take each dose with about 1 cup of water within 30 minutes after a meal, preferably breakfast.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Given by PO

Revumenib

Intervention Type: DRUG

Given by PO

Interventions

Venetoclax

Given by PO

Intervention Type: DRUG

Revumenib

Given by PO

Intervention Type: DRUG

Other Intervention Names

ABT-199; GDC-0199; SNDX-5613

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 12 years with weight ≥ 45Kg.

2. ECOG performance status of ≤ 2. (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and <18 years); Lansky Performance Score of ≥50 (if aged <16 years).

3. Leukemia status:

• Known history of NPM1mt, or KMT2Ar, or NUP98r AML.
• Bone marrow assessment showing no leukemia by morphology (blasts <5%) in first remission following high intensity chemotherapy or at least 2 cycles of low intensity therapy (e.g. hypomethylating agent or low-dose cytarabine-based), or in second remission following any therapy, with MRD ≥ 0.1% identified by multiparameter flow cytometry using central lab testing.
• No clinically active extramedullary disease.

4. Baseline ejection fraction must be > 40%.

5. Adequate hepatic function (direct bilirubin < 1.5x upper limit of normal (ULN) unless increase is due leukemic involvement, and AST and/or ALT < 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5x ULN will be considered eligible).

6. Adequate renal function with an estimated glomerular filtration rate ≥ 60 mL/min based on local institutional practice for age-appropriate determination.

7. Able to swallow pills.

8. Participants or parent/guardian is willing and able to provide informed consent. Interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy, whichever is shorter. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.

9. Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study and at least 3 months after the last treatment.

Exclusion Criteria

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syndax Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ghayas Issa, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: RECRUITING

Dana-Farber Cancer Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ghayas Issa, MD

Role: CONTACT

gcissa@mdanderson.org

(713) 745-6798

Facility Contacts

Alexander Ambinder, MD

Role: primary

aambind1@jhmi.edu

Jacqueline Garcia, MD

Role: primary

jacqueline_garcia@dfci.harvard.edu

Aaron Goldberg, MD

Role: primary

goldbera@mskcc.org

646-608-3752

Ghayas Issa, MD

Role: primary

gcissa@mdanderson.org

713-745-6798

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

NCI-2024-01721

Identifier Type: OTHER

Identifier Source: secondary_id

2023-0794

Identifier Type: -

Identifier Source: org_study_id