NCT07223814Recruiting

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

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.

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

The trial team's contact details are shown on request.

See the official trial record

Status: Recruiting
Phase: Phase 3
Study type: Interventional
Countries: Switzerland, Germany, Austria, United States, Australia, Belgium, Estonia, Finland, Japan, Netherlands, Norway, Spain, Sweden
Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland(Other)
Protocol no.: HOVON 181 AML
Conditions: Acute Myeloid Leukemia
Interventions: Drug

Treatments studied

Bleximenib
Cytarabine
Daunorubicin or Idarubicin
Placebo

Collaborators

German-Austrian Acute Myeloid Leukemia Study Group

Locations · 98

Bern, SwitzerlandCH-Bern-INSELRecruiting at this site
Fribourg, SwitzerlandCH-Fribourg-HFRRecruiting at this site
Geneva, SwitzerlandCH-Geneve (14)-HCUGERecruiting at this site
Sankt Gallen, SwitzerlandCH-St. Gallen-KSSGRecruiting at this site
Zurich, SwitzerlandCH-Zürich-USZRecruiting at this site
Aachen, GermanyDE-Aachen-UKAACHENRecruiting at this site
Bochum, GermanyDE-Bochum-RUBRecruiting at this site
Bonn, GermanyDE-Bonn-UNIBONNRecruiting at this site
Braunschweig, GermanyDE-Braunschweig-KLINIKUMBRAUNSCHWEIGRecruiting at this site
Greifswald, GermanyDE-Greifswald-UNIGREIFSWALDRecruiting at this site
Halle, GermanyDE-Halle-UMHRecruiting at this site
Hamburg, GermanyDE-Hamburg-ASKLEPIOSSTGEORGRecruiting at this site
Hanover, GermanyDE-Hannover-MHHANNOVERRecruiting at this site
Heilbronn, GermanyDE-Heilbronn-SLKRecruiting at this site
Homburg, GermanyDE-Homburg-UNIKLINIKSAARLANDRecruiting at this site
Karlsruhe, GermanyDE-Karlsruhe-KLINIKUMKARLSRUHERecruiting at this site
Oldenburg, GermanyDE-Oldenburg-KLINIKUMOLDENBURGRecruiting at this site
Passau, GermanyDE-Passau-KLINIKUMPASSAURecruiting at this site
Rostock, GermanyDE-Rostock-MUROSTOCKRecruiting at this site
Ulm, GermanyDE-Ulm-UNIKLINKULMRecruiting at this site
Linz, AustriaAT-Linz-ORDENSKLINIKUMRecruiting at this site
Los Angeles, United StatesUS-Los Angeles CA-UCLARecruiting at this site
San Francisco, United StatesUS-San Francisco CA-UCSFRecruiting at this site
Orlando, United StatesUS-Orlando FL-ORLANDOHEALTHRecruiting at this site
Atlanta, United StatesUS-Atlanta GA-EMORYRecruiting at this site
Chicago, United StatesUS-Chigago IL-UHCHICAGORecruiting at this site
Kansas City, United StatesUS-Kansas City KS-KUMCRecruiting at this site
Baltimore, United StatesUS-Baltimore MD-UMGCCCRecruiting at this site
St Louis, United StatesUS-St Louis MO-WASHURecruiting at this site
Charlotte, United StatesUS-Charlotte NC-NOVANTCHARLOTTERecruiting at this site

In total, worldwide, all 98 sites listed in the registry are recruiting.

Site status per the ClinicalTrials.gov registry (last update posted: October 8, 2026).

This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.

+ 68 more locations

Other identifiers

2025-522767-15-00 · CTIS number
2025 · NIH grant

Other versions

These results are indicative and do not replace medical advice — discuss them with your doctor.