Health Trials

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

ConditionAcute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorStichting Hemato-Oncologie voor Volwassenen Nederland

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

≥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.

Disqualifiers

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.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bleximenib

    Drug

    Participants will receive bleximenib

  • Cytarabine

    Drug

    Participants will receive Cytarabine

  • Daunorubicin or Idarubicin

    Drug

    Participants will receive Daunorubicin or Idarubicin

  • Placebo

    Drug

    Participants will receive Placebo

Treatment groups

875 Participants
are divided into 3 treatment groups
Group A: Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenibExperimental treatment 3 interventions
Group B: Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.Experimental treatment 4 interventions
Group C: Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.Placebo comparator 3 interventions

Trial outcomes

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.

Time frame
Up to 4 years and 5 months

Secondary outcomes

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.

Time frame
Up to 7 years and 10 months
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.

Time frame
Up to 7 years and 10 months
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.

Time frame
Up to 4 years and 5 months
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

Time frame
Up to 7 years and 10 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stichting Hemato-Oncologie voor Volwassenen Nederland

Lead sponsor

German-Austrian Acute Myeloid Leukemia Study Group

Collaborator

Source ClinicalTrials.gov
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