Bleximenib in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for Treatment of Patients With Acute Myeloid Leukemia (AML)
Bleximenib or Placebo in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for the Treatment of Patients With Newly Diagnosed KMT2A-rearranged or NPM1-mutant Acute Myeloid Leukemia Eligible for Intensive Chemotherapy: a Double-blind Phase 3 Study
2 other identifiers
interventional
875
8 countries
43
Brief Summary
The current standard of care treatment for adult patients with acute myeloid leukemia (AML) consists of chemotherapy and, if indicated, donor stem cell transplantation. Bleximenib blocks the interaction between a protein called menin and another protein called KMT2A in the leukemia cells. When this interaction is disrupted in AML with mutations in the NPM1 or KMT2A gene, bleximenib can cause leukemia cells to die. The main objective is to assess if treatment with bleximenib, when added to chemotherapy treatment will improve treatment outcome in adult participants with newly diagnosed AML who present with mutations in the NPM1 or KMT2A genes. This is a randomized, double-blind, placebo-controlled, phase 3 clinical trial. All of the participants will receive standard chemotherapy treatment, combined with either bleximenib or a placebo. A placebo is a substance that looks like the study medicine but has no active ingredients (e.g., a sugar pill). In a double blind trial neither the participant nor the doctor know if placebo or active study drug is given. After the end of the protocol treatment there will be an observational follow-up of 4 years from the time of inclusion of the last patient. The results of the different treatment groups will be compared. 875 previously untreated patients with AML with a specific change in the DNA of the leukemia cells (a KMT2A rearrangement or a NPM1 mutation) will be included. Participants must be 18 years or older and considered eligible for intensive chemotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2026
Longer than P75 for phase_3
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 30, 2025
CompletedFirst Posted
Study publicly available on registry
November 3, 2025
CompletedStudy Start
First participant enrolled
March 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2033
July 14, 2026
July 1, 2026
4.3 years
October 30, 2025
July 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event-Free Survival (EFS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
To assess if treatment with bleximenib, as compared with placebo, in combination with remission induction chemotherapy, prolongs event-free survival (EFS) measured from the time from randomization to failure to achieve CR after remission induction, hematologic relapse after achieving CR, or death, whichever occurs first.
Up to 4 years and 5 months
Secondary Outcomes (4)
Overall Survival (OS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
Up to 7 years and 10 months
Rates of CR, CRh, CRi in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
Up to 7 years and 10 months
Prolongation of CR (DoCR) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
Up to 4 years and 5 months
Percentage of participants undergoing an allo-SCT in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
Up to 7 years and 10 months
Study Arms (3)
Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib
EXPERIMENTALBleximenib in combination with remission induction and consolidation therapy, followed by bleximenib maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.
EXPERIMENTALBleximenib in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.
PLACEBO COMPARATORPlacebo comparator in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy . Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
Interventions
Participants will receive bleximenib
Participants will receive Cytarabine
Participants will receive Daunorubicin or Idarubicin
Participants will receive Placebo
Eligibility Criteria
You may qualify if:
- ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.
- New diagnosis of AML (≥10% blasts in BM or peripheral blood) with mutated NPM1 or with recurring rearrangements involving KMT2A according to ICC 2022 criteria.
- Considered eligible for intensive chemotherapy.
- WHO/ECOG performance status ≤2.
- Adequate renal and hepatic functions prior to randomization.
You may not qualify if:
- Prior (chemo-)therapy for AML, including prior treatment with hypomethylating agents
- Known active leukemic involvement of the central nervous system (CNS).
- Recipient of solid organ transplant.
- Cardiac disease:
- Any of the following within 6 months of randomization: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (NYHA Class III or IV), uncontrolled or symptomatic arrhythmias, stroke, or transient ischemic attack.
- QTc interval using Fridericia's formula (QTcF) ≥470 ms. Prolonged QTc interval associated with bundle branch block or pacemaking is permitted.
- Left ventricular ejection fraction (LVEF) \<40% by ECHO or MUGA scan obtained within 28 days prior to the start of study treatment.
- Previously received cumulative dose of any combination of anthracyclines or anthracenediones of ≥500 mg/m2.
- Chronic respiratory disease requiring supplemental oxygen.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (43)
US-San Francisco CA-UCSF
San Francisco, California, 94115, United States
US-Atlanta GA-EMORY
Atlanta, Georgia, 30322, United States
US-Kansas City KS-KUMC
Kansas City, Kansas, 66103, United States
US-Baltimore MD-UMGCCC
Baltimore, Maryland, 21201, United States
US-St Louis MO-WASHU
St Louis, Missouri, 63110, United States
US-Cincinnati OH-CINCY
Cincinnati, Ohio, 45219, United States
AU-Adelaide-FLINDERS
Adelaide, Australia
AU-Adelaide-RAH
Adelaide, Australia
AU-Birtinya-SUNSHINECOAST
Birtinya, Australia
AU-Brisbane-PAH
Brisbane, Australia
AU-Camperdown-RPA
Camperdown, Australia
AU-Melbourne-AUSTIN
Melbourne, Australia
AU-Melbourne-PMCC
Melbourne, Australia
AU-Sydney-WSAH
Sydney, Australia
BE-Antwerpen-ZAS
Antwerp, Belgium
Be-Charleroi-GHDC
Charleroi, Belgium
BE-Geel-STDIMPNA
Geel, Belgium
BE-Gent-UZGENT
Ghent, Belgium
BE-Haine-Saint-Paul-JOLIMONT
Jolimont, Belgium
BE-Liege-CHULIEGE
Liège, Belgium
BE-Liege-MONTLEGIA
Liège, Belgium
BE-Yvoir-MONTGODINNE
Yvoir, Belgium
FI-Oulu-OYS
Oulu, Finland
DE-Bochum-RUB
Bochum, Germany
DE-Greifswald-UNIGREIFSWALD
Greifswald, Germany
DE-Passau-KLINIKUMPASSAU
Passau, Germany
DE-Ulm-UNIKLINKULM
Ulm, Germany
JP-Nagasaki Shi-NAGASAKI
Nagasaki, Japan
NL-Amersfoort-MEANDERMC
Amersfoort, Netherlands
NL-Amsterdam-AMSTERDAMUMC
Amsterdam, Netherlands
NL-Amsterdam-OLVG
Amsterdam, Netherlands
NL-Arnhem-RIJNSTATE
Arnhem, Netherlands
NL-Breda-AMPHIA
Breda, Netherlands
NL-Dordrecht-ASZ
Dordrecht, Netherlands
NL-Eindhoven-MAXIMAMC
Eindhoven, Netherlands
NL-Groningen-UMCG
Groningen, Netherlands
NL-Leeuwarden-FRISIUSMC
Leeuwarden, Netherlands
NL-Leiden-LUMC
Leiden, Netherlands
NL-Nieuwegein-ANTONIUS
Nieuwegein, Netherlands
NL-Nijmegen-RADBOUD
Nijmegen, Netherlands
NL-Rotterdam-ERASMUCMC
Rotterdam, Netherlands
NL-Den Haag-HAGA
The Hague, Netherlands
SE-Lund-Suh
Lund, Sweden
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
M.H.G.P. Raaijmakers
Erasmus Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 30, 2025
First Posted
November 3, 2025
Study Start
March 1, 2026
Primary Completion (Estimated)
June 1, 2030
Study Completion (Estimated)
December 1, 2033
Last Updated
July 14, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- After the publication of primary endpoint analysis
According to the current publication policy the protocol and Statistica! Analysis Plan ( SAP) will be shared. The principal lnvestigators can be contacted for IPD sharing after the publication of the study results. According to 'HOVON sample and/or Data request Form' theHOVON director; chair of theHOVON Acute Myeloid Leukemie working group, the study PI and Coordinating lnvestigator should approve data/sample sharing.