Home › Trials › NCT06852222

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

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

Phase 3 Interventional Janssen Research & Development, LLC · NCT06852222

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.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorJanssen Research & Development, LLC Industry-sponsored
Drugs / interventionschemotherapy
Locations248 sites (Birmingham, Alabama and 247 other locations)
Trial IDNCT06852222 on ClinicalTrials.gov

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.

Who should consider this trial

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.

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.

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 performed: 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.

Eligibility criteria

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 this trial is running

Birmingham, Alabama and 247 other locations

+198 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Leukemia, Myeloid, Acute
Last reviewed 2026-06-10 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.