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

NCT07223814 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: HOVON 181 AML2025-522767-15-00
• Study Type: interventional
• Target: 875
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML; adult; newly diagnosed AML; NPM1; KMT2A

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

EXPERIMENTAL

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; Drug: Cytarabine; Drug: Daunorubicin or Idarubicin

Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.

EXPERIMENTAL

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; Drug: Cytarabine; Drug: Daunorubicin or Idarubicin; Drug: Placebo

Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.

PLACEBO COMPARATOR

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; Drug: Daunorubicin or Idarubicin; Drug: Placebo

Interventions

Bleximenib DRUG

Participants will receive bleximenib

Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib; Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.

Cytarabine DRUG

Participants will receive Cytarabine

Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib; Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.; Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.

Daunorubicin or Idarubicin DRUG

Participants will receive Daunorubicin or Idarubicin

Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib; Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.; Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.

Placebo DRUG

Participants will receive Placebo

Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.; Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead
• German-Austrian Acute Myeloid Leukemia Study Group: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Daunorubicin; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

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: December 1, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 1, 2033
• Last Updated: November 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After the publication of primary endpoint analysis