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

NCT06284486 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0794NCI-2024-01721
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (1)

Venetoclax + Revumenib

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Revumenib

Interventions

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

Venetoclax + Revumenib

Revumenib DRUG

Given by PO

Also known as: SNDX-5613

Venetoclax + Revumenib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 12 years with weight ≥ 45Kg.
• 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).
• 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.
• Baseline ejection fraction must be \> 40%.
• 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).
• Adequate renal function with an estimated glomerular filtration rate ≥ 60 mL/min based on local institutional practice for age-appropriate determination.
• Able to swallow pills.
• 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.
• 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.

You may not qualify if:

• Prior treatment with a menin inhibitor.
• Participants who are expected to receive standard therapy (either intensive or hypomethylating agent and venetoclax) with continued tolerability and benefit.
• Participants who are expected to be able to proceed with stem cell transplantation within the next 30 days.
• Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
• 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.
• Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
• Participants with a concurrent active malignancy under treatment.
• Known active hepatitis B (HBV) or Hepatitis C (HCV) or HIV infection.
• Female subjects who are pregnant or breast-feeding.
• Participant has an active uncontrolled infection.
• 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.
• QTc \>450 msec for males and QTc \>470 msec for females using the Fridericia Formula.
• 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.
• Clinically active central nervous system (CNS) leukemia.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Syndax Pharmaceuticals: collaborator
• AbbVie: collaborator

Study Sites (4)

Johns Hopkins University

Baltimore, Maryland, 21218, United States

RECRUITING

Dana-Farber Cancer Center

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; revumenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Ghayas Issa, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ghayas Issa, MD

CONTACT

(713) 745-6798; gcissa@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: February 29, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (4)