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RecruitingLast updated: 12 June 2026

HOVON-181: Evaluating whether adding a targeted drug called bleximenib to standard chemotherapy is effective for people with newly diagnosed acute myeloid leukaemiaBleximenib 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Blood Cancers Haematological

Age

People18+

Trial acronym

HOVON-181

Clinical summary

Summary

The current standard of care treatment for adults with acute myeloid leukaemia (AML) consists of chemotherapy and, if indicated, donor stem cell transplantation.

Bleximenib is a drug that blocks the interaction between a protein called menin and another protein called KMT2A in the leukaemia cells. When this interaction is disrupted in AML with mutations in the NPM1 or KMT2A gene, bleximenib can cause leukaemia cells to die.

The main objective is to assess if treatment with bleximenib, when added to chemotherapy treatment, will improve treatment outcomes in people with newly diagnosed AML who present with mutations in the NPM1 or KMT2A genes.

How the study works
Eligible participants will receive standard chemotherapy treatment, which will be combined with either bleximenib or a placebo. People will be randomly assigned (by chance) to receive either bleximenib or the placebo.

A placebo is a substance that looks like the study medicine but has no active ingredients (e.g. a sugar pill). This is a double blind trial, which means neither the participants 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.

Conditions

This trial is treating people with newly diagnosed acute myeloid leukaemia with either MPM1 or KMT2A mutations

Eligibility

Inclusion

  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

  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.

Inclusion

  • You have been diagnosed with cancer, but have not received any treatment.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

  • NCT07223814 *
  • 2025-522767-15-00 *
  • HOVON 181 AML; ALLG AMLM3

Trial sponsor

Stichting Hemato-Oncologie voor Volwassenen Nederland

Scientific Title

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

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