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

NCT ID: NCT07223814

Last Updated: 2025-11-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 875 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2033-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: EXPERIMENTAL

Bleximenib

Intervention Type: DRUG

Participants will receive bleximenib

Cytarabine

Intervention Type: DRUG

Participants will receive Cytarabine

Daunorubicin or Idarubicin

Intervention Type: DRUG

Participants will receive Daunorubicin or Idarubicin

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)

Group Type: EXPERIMENTAL

Bleximenib

Intervention Type: DRUG

Participants will receive bleximenib

Cytarabine

Intervention Type: DRUG

Participants will receive Cytarabine

Daunorubicin or Idarubicin

Intervention Type: DRUG

Participants will receive Daunorubicin or Idarubicin

Placebo

Intervention Type: DRUG

Participants will receive Placebo

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)

Group Type: PLACEBO_COMPARATOR

Cytarabine

Intervention Type: DRUG

Participants will receive Cytarabine

Daunorubicin or Idarubicin

Intervention Type: DRUG

Participants will receive Daunorubicin or Idarubicin

Placebo

Intervention Type: DRUG

Participants will receive Placebo

Interventions

Bleximenib

Participants will receive bleximenib

Intervention Type: DRUG

Cytarabine

Participants will receive Cytarabine

Intervention Type: DRUG

Daunorubicin or Idarubicin

Participants will receive Daunorubicin or Idarubicin

Intervention Type: DRUG

Placebo

Participants will receive Placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German-Austrian Acute Myeloid Leukemia Study Group

UNKNOWN

Sponsor Role: collaborator

Stichting Hemato-Oncologie voor Volwassenen Nederland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

2025-522767-15-00

Identifier Type: CTIS

Identifier Source: secondary_id

HOVON 181 AML

Identifier Type: -

Identifier Source: org_study_id