Clinical trial Recruiting at 270 sites Phase 3 Interventional Ages 18 and up

Bleximenib added to venetoclax and azacitidine for newly diagnosed NPM1- or KMT2A-mutated AML

Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2A Rearrangements or NPM1 Mutations Who Are Ineligible for Intensive Chemotherapy

Run by Janssen Research & Development, LLC · NCT06852222 · Data updated 2026-11-12

This trial will test whether adding bleximenib to venetoclax plus azacitidine helps people with newly diagnosed AML that has NPM1 or KMT2A mutations who cannot have intensive chemotherapy.

More Leukemia, Myeloid, Acute trials

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment600 (estimated)
SponsorJanssen Research & Development, LLC
Industry-sponsored
Drugs / interventionschemotherapy
Locations270 sites (Birmingham, Alabama and 269 other locations)
StatusRecruiting
StartedJune 4, 2025
Main results expectedJune 22, 2029
Study endsAugust 15, 2029
Registry record updatedNovember 3, 2026
Trial IDNCT06852222 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults (≥18 years) with newly diagnosed AML carrying NPM1 mutation or KMT2A rearrangement who are considered ineligible for intensive chemotherapy and have ≥10% bone marrow blasts.

Probably not a fit

Patients without NPM1 or KMT2A alterations, those eligible for standard intensive chemotherapy, or those who have already received prior AML therapy are unlikely to benefit from this trial.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 3, randomized trial compares bleximenib plus venetoclax and azacitidine versus placebo plus venetoclax and azacitidine in adults with newly diagnosed AML harboring NPM1 mutations or KMT2A rearrangements who are ineligible for intensive chemotherapy. Participants must have at least 10% bone marrow blasts and meet age or comorbidity criteria that preclude intensive chemo. Enrolled patients receive the assigned drug combination and are followed for response, survival, and safety outcomes. The study aims to determine whether adding bleximenib improves clinical outcomes without unacceptable toxicity.

Why it matters

Potential benefit: If successful, adding bleximenib could increase remission rates or extend survival for patients with NPM1- or KMT2A-mutated AML who cannot tolerate intensive chemotherapy.

How similar studies have gone: Early-phase trials of menin inhibitors combined with venetoclax or hypomethylating agents have shown promising activity in NPM1- and KMT2A-mutant AML, but confirmatory phase 3 evidence is still limited.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion criteria:

* Be 18 years of age or older at the time of informed consent
* Previously untreated lysine N-methyltransferase 2A gene rearranged (KMT2Ar) or nucleophosmin 1 gene mutated (NPM1m) acute myeloid leukemia (AML) with greater than or equal to (\> or =) 10% bone marrow blasts per 2022 international Consensus Classification criteria
* Ineligible for intensive chemotherapy based on the following criteria: a) \>= 75 years of age and ineligible per physician's discretion, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, b) \>=18 to \<75 years of age with \>= 1 of the following comorbidities: i) ECOG performance status of 2, ii) Severe cardiac disorder, iii) Severe pulmonary disorder, iv) Renal impairment, v) Moderate hepatic impairment vi) Comorbidity that, in the investigator's opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented before enrollment as defined in the protocol. Ineligibility for intensive chemotherapy should be explicitly approved by a multidisciplinary team in countries in which this process is standard of care
* Participants must have adequate hepatic and renal function
* A female participant must agree not to be pregnant, breast-feed, plan to become pregnant and use protocol-specified contraception while enrolled in this study and for 6 months after the last dose of study treatment
* A male participant must agree to use protocol-specified contraception while enrolled in this study for at least 90 days after the last dose of study treatment
* Must sign an informed consent form indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study

Exclusion criteria:

* Diagnosis of acute promyelocytic leukemia (APL)
* Known active leukemic involvement of the central nervous system (CNS)
* Recipient of solid organ transplant
* Any cardiac disorders such as heart attack, uncontrolled/unstable chest pain, congestive heart failure, uncontrolled or symptomatic irregular heartbeat, blockage of a blood vessel to brain, or transient ischemic (decreased oxygen in tissue) attack within 6 months of randomization
* Active infectious hepatitis
* Live, attenuated vaccine within 4 weeks of randomization
* Known allergies, hypersensitivity, or intolerance of bleximenib, azacitidine, or venetoclax excipients

Where it's running

  • University of Alabama at Birmingham
    Birmingham, Alabama, United States
    Recruiting
  • Cancer Treatment Center of America Phoenix
    Goodyear, Arizona, United States
    Recruiting
  • The University of Arizona Cancer Center
    Tucson, Arizona, United States
    Recruiting
  • University of Arkansas at Little Rock
    Little Rock, Arkansas, United States
    Recruiting
  • City of Hope
    Duarte, California, United States
    Recruiting
  • City of Hope Orange County Lennar Foundation Cancer Center
    Irvine, California, United States
    Recruiting
Show 44 more locations
  • Rocky Mountain Cancer Centers
    Aurora, Colorado, United States
    Recruiting
  • Medical Oncology Hematology Consultants, PA
    Newark, Delaware, United States
    Recruiting
  • Florida Cancer Specialists & Research Institute
    Fort Myers, Florida, United States
    Recruiting
  • Jupiter Research
    Jupiter, Florida, United States
    Recruiting
  • AdventHealth Medical Group Blood & Marrow Transplant at Orlando
    Orlando, Florida, United States
    Recruiting
  • Orlando Health Cancer Institute
    Orlando, Florida, United States
    Recruiting
  • Memorial Cancer Institute
    Pembroke Pines, Florida, United States
    Recruiting
  • Moffit Cancer center
    Tampa, Florida, United States
    Recruiting
  • Cleveland Clinic Florida
    Weston, Florida, United States
    Recruiting
  • University of Chicago Medicine
    Chicago, Illinois, United States
    Recruiting
  • Illinois Cancer Specialists
    Niles, Illinois, United States
    Recruiting
  • University of Kentucky Markey Cancer Center
    Lexington, Kentucky, United States
    Recruiting
  • UofL Health Brown Cancer Center
    Louisville, Kentucky, United States
    Recruiting
  • Norton Cancer Institute
    Louisville, Kentucky, United States
    Recruiting
  • Mary Bird Perkins Cancer Center
    Baton Rouge, Louisiana, United States
    Recruiting
  • MaineHealth Institute for Research
    South Portland, Maine, United States
    Recruiting
  • Center for Cancer and Blood Disorders
    Bethesda, Maryland, United States
    Recruiting
  • Dana Farber Cancer Institute
    Boston, Massachusetts, United States
    Recruiting
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts, United States
    Recruiting
  • Henry Ford Health System
    Detroit, Michigan, United States
    Recruiting
  • Trinity Health Michigan Heart - Ann Arbor Campus
    Ypsilanti, Michigan, United States
    Recruiting
  • Washington University in St Louis
    St Louis, Missouri, United States
    Recruiting
  • Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire, United States
    Recruiting
  • John Theurer Cancer Center at Hackensack University Medical Center
    Hackensack, New Jersey, United States
    Recruiting
  • Roswell Park Comprehensive Cancer Center
    Buffalo, New York, United States
    Recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York, United States
    Recruiting
  • New York Presbyterian - Weill Cornell
    New York, New York, United States
    Recruiting
  • University of Rochester Medical Center
    Rochester, New York, United States
    Recruiting
  • Einstein-Montefiore Medical Center
    The Bronx, New York, United States
    Recruiting
  • Atrium Health
    Charlotte, North Carolina, United States
    Recruiting
  • Novant Health Charlotte
    Charlotte, North Carolina, United States
    Recruiting
  • Carolina Oncology Specialists
    Charlotte, North Carolina, United States
    Recruiting
  • Novant Health Winston Salem
    Winston-Salem, North Carolina, United States
    Recruiting
  • Atrium Health Wake Forest Baptist Comprehensive Cancer Center
    Winston-Salem, North Carolina, United States
    Recruiting
  • Gabrail Cancer Center
    Canton, Ohio, United States
    Recruiting
  • Miami Valley Hospital South
    Centerville, Ohio, United States
    Recruiting
  • Oncology Hematology Care
    Cincinnati, Ohio, United States
    Recruiting
  • University Hospitals Cleveland Medical Center
    Cleveland, Ohio, United States
    Recruiting
  • Cleveland Clinic
    Cleveland, Ohio, United States
    Recruiting
  • Providence Portland Medical Center
    Portland, Oregon, United States
    Recruiting
  • Providence Oncology and Hematology Care Clinic Westside
    Portland, Oregon, United States
    Recruiting
  • Thomas Jefferson University
    Philadelphia, Pennsylvania, United States
    Recruiting
  • Fox Chase Cancer Center
    Philadelphia, Pennsylvania, United States
    Recruiting
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania, United States
    Recruiting

+220 more sites. See ClinicalTrials.gov for the full list.

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.