Bleximenib in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for Treatment of Patients With Acute Myeloid Leukemia (AML)

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2026 by Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
Information Provided by (Responsible Party)
Stichting Hemato-Oncologie voor Volwassenen Nederland
Clinicaltrials.gov Identifier
NCT07223814
Other Study ID Numbers:
HOVON 181 AML
First Submitted
October 29, 2025
First Posted
November 2, 2025
Last Update Posted
August 31, 2026
Last Verified
July 2026

ClinicalTrials.gov processed this data on August 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Acute Myeloid Leukemia
Drug: BleximenibDrug: BleximenibDrug: Cytarabine

Study Design

Study TypeInterventional
Actual Enrollment875 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleBleximenib 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
Study Start DateFebruary 28, 2026
Actual Primary Completion Date3yrs 8mos from now
Actual Study Completion Date7yrs 2mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib
Bleximenib 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)
Drug: Bleximenib
Participants will receive bleximenib
Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.
Bleximenib 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)
Drug: Bleximenib
Participants will receive bleximenib
Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.
Placebo 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)
Drug: Cytarabine
Participants will receive Cytarabine

Outcome Measures

Primary Outcome Measures
  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.
Secondary Outcome Measures
  1. Overall Survival (OS) 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 and consolidation chemotherapy, followed by maintenance therapy, prolongs overall survival (OS) measured from randomization to death due to any cause.
  2. Rates of CR, CRh, CRi in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
    Defined as the proportion of participants achieving a given response after induction cycle 1 and after induction cycle 2.
  3. Prolongation of CR (DoCR) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
    Defined as the time from achieving first response of CR to hematologic relapse or death from any cause, whichever occurs first.
  4. Percentage of participants undergoing an allo-SCT in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
    To assess the percentage of participants undergoing an allo-SCT as part of protocol treatment

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. ≥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. 2. 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. 3. Considered eligible for intensive chemotherapy. 4. WHO/ECOG performance status ≤2. 5. Adequate renal and hepatic functions prior to randomization.
Exclusion Criteria
1. Prior (chemo-)therapy for AML, including prior treatment with hypomethylating agents 2. Known active leukemic involvement of the central nervous system (CNS). 3. Recipient of solid organ transplant. 4. Cardiac disease: 1. 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. 2. QTc interval using Fridericia's formula (QTcF) ≥470 ms. Prolonged QTc interval associated with bundle branch block or pacemaking is permitted. 3. Left ventricular ejection fraction (LVEF) \<40% by ECHO or MUGA scan obtained within 28 days prior to the start of study treatment. 4. Previously received cumulative dose of any combination of anthracyclines or anthracenediones of ≥500 mg/m2. 5. Chronic respiratory disease requiring supplemental oxygen.

Contacts and Locations

Sponsors and CollaboratorsStichting Hemato-Oncologie voor Volwassenen Nederland
Locations
US-Los Angeles CA-UCLA | Los Angeles California, United States, 90095US-San Francisco CA-UCSF | San Francisco California, United States, 94115US-Orlando FL-ORLANDOHEALTH | Orlando Florida, United States, 32806US-Atlanta GA-EMORY | Atlanta Georgia, United States, 30322US-Chigago IL-UHCHICAGO | Chicago Illinois, United States, 60637US-Kansas City KS-KUMC | Kansas City Kansas, United States, 66103US-Baltimore MD-UMGCCC | Baltimore Maryland, United States, 21201US-St Louis MO-WASHU | St Louis Missouri, United States, 63110US-Cincinnati OH-CINCY | Cincinnati Ohio, United States, 45219US-Colombus OH-OSU | Columbus Ohio, United States, 43210US-Pittsburgh PA-PITT | Pittsburgh Pennsylvania, United States, 15260AU-Adelaide-FLINDERS | Adelaide , Australia, AU-Adelaide-RAH | Adelaide , Australia, AU-Birtinya-SUNSHINECOAST | Birtinya , Australia, AU-Brisbane-PAH | Brisbane , Australia, AU-Brisbane-RBWH | Brisbane , Australia, AU-Camperdown-RPA | Camperdown , Australia, AU-Melbourne-AUSTIN | Melbourne , Australia, AU-Melbourne-MONASH | Melbourne , Australia, AU-Melbourne-PMCC | Melbourne , Australia, AU-Sydney-WSAH | Sydney , Australia, AT-Linz-ORDENSKLINIKUM | Linz , Austria, BE-Antwerpen-UZA | Antwerp , Belgium, BE-Antwerpen-ZAS | Antwerp , Belgium, BE-Brugge-AZBRUGGE | Bruges , Belgium, BE-Brussel-BORDET | Brussels , Belgium, BE-Bruxelles-STLUC | Brussels , Belgium, Be-Charleroi-GHDC | Charleroi , Belgium, BE-Geel-STDIMPNA | Geel , Belgium, BE-Gent-UZGENT | Ghent , Belgium, BE-Hasselt-VIRGAJESSE (Jessa Ziekenhuis) | Hasselt , Belgium, BE-Haine-Saint-Paul-JOLIMONT | Jolimont , Belgium, BE-Leuven-UZLEUVEN | Leuven , Belgium, BE-Liege-CHULIEGE | Liège , Belgium, BE-Liege-MONTLEGIA | Liège , Belgium, BE-Yvoir-MONTGODINNE | Yvoir , Belgium, EE-Tallinn-REGIONAALHAIGLA | Tallinn , Estonia, EE-Tartu-TARTU | Tartu , Estonia, FI-Helsinki-HUS | Helsinki , Finland, FI-Kuopio-KYS | Kuopio , Finland, FI-Oulu-OYS | Oulu , Finland, FI-Tampere-TAYS | Tampere , Finland, DE-Aachen-UKAACHEN | Aachen , Germany, DE-Bochum-RUB | Bochum , Germany, DE-Bonn-UNIBONN | Bonn , Germany, DE-Greifswald-UNIGREIFSWALD | Greifswald , Germany, DE-Halle-UMH | Halle , Germany, DE-Hannover-MHHANNOVER | Hanover , Germany, DE-Heilbronn-SLK | Heilbronn , Germany, DE-Karlsruhe-KLINIKUMKARLSRUHE | Karlsruhe , Germany, DE-Oldenburg-KLINIKUMOLDENBURG | Oldenburg , Germany, DE-Passau-KLINIKUMPASSAU | Passau , Germany, DE-Rostock-MUROSTOCK | Rostock , Germany, DE-Ulm-UNIKLINKULM | Ulm , Germany, JP-Chuo-Ku-CHIBA | Chūōku , Japan, JP-Maebashi-Shi-GUNMA | Maebashi , Japan, JP-Nagasaki Shi-NAGASAKI | Nagasaki , Japan, JP-Nishi-Gun-YAMAGATA | Yamagata , Japan, JP-Yoshida-Gun-FUKUI | Yoshida , 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-Maastricht-MUMC | Maastricht , Netherlands, NL-Nieuwegein-ANTONIUS | Nieuwegein , Netherlands, NL-Nijmegen-RADBOUD | Nijmegen , Netherlands, NL-Rotterdam-ERASMUCMC | Rotterdam , Netherlands, NL-Den Haag-HAGA | The Hague , Netherlands, NL-Zwolle-ISALA | Zwolle , Netherlands, ES-Palma-SSIB | Palma de Mallorca , Spain, SE-Lund-Suh | Lund , Sweden, CH-Bern-INSEL | Bern , Switzerland, CH-Fribourg-HFR | Fribourg , Switzerland, CH-Geneve (14)-HCUGE | Geneva , Switzerland, CH-St. Gallen-KSSG | Sankt Gallen , Switzerland, CH-Zürich-USZ | Zurich , Switzerland,
Investigators
Principal Investigator: M.H.G.P. Raaijmakers, Erasmus Medical Center