Bleximenib in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for Treatment of Patients With Acute Myeloid Leukemia (AML)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Bleximenib, Cytarabine, Daunorubicin or Idarubicin, Placebo.
- Who it may be relevant to
- Registry conditions: Acute Myeloid Leukemia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia, Belgium, Estonia, Finland +4
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official 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
Overview
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.
Interventions
- Drug Bleximenib
Participants will receive bleximenib - Drug Cytarabine
Participants will receive Cytarabine - Drug Daunorubicin or Idarubicin
Participants will receive Daunorubicin or Idarubicin - Drug Placebo
Participants will receive Placebo
Primary outcome measures
- Event-Free Survival (EFS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy [Time frame: Up to 4 years and 5 months]
Secondary outcome measures (4)
- Overall Survival (OS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Up to 7 years and 10 months]
Eligibility criteria
Inclusion criteria
- ≥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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Double blind
- Primary purpose
- Treatment
Study locations
Netherlands · 15 centers
- NL-Amersfoort-MEANDERMC — Amersfoort
- NL-Amsterdam-AMSTERDAMUMC — Amsterdam
- NL-Amsterdam-OLVG — Amsterdam
- NL-Arnhem-RIJNSTATE — Arnhem
- NL-Breda-AMPHIA — Breda
- NL-Dordrecht-ASZ — Dordrecht
- NL-Eindhoven-MAXIMAMC — Eindhoven
- NL-Groningen-UMCG — Groningen
- … and 7 more centers
Belgium · 12 centers
- BE-Antwerpen-UZA — Antwerp
- BE-Antwerpen-ZAS — Antwerp
- BE-Brugge-AZBRUGGE — Bruges
- BE-Brussel-BORDET — Brussels
- Be-Charleroi-GHDC — Charleroi
- BE-Geel-STDIMPNA — Geel
- BE-Gent-UZGENT — Ghent
- BE-Haine-Saint-Paul-JOLIMONT — Jolimont
- … and 4 more centers
Germany · 10 centers
- DE-Aachen-UKAACHEN — Aachen
- DE-Bochum-RUB — Bochum
- DE-Bonn-UNIBONN — Bonn
- DE-Greifswald-UNIGREIFSWALD — Greifswald
- DE-Halle-UMH — Halle
- DE-Hannover-MHHANNOVER — Hanover
- DE-Heilbronn-SLK — Heilbronn
- DE-Karlsruhe-KLINIKUMKARLSRUHE — Karlsruhe
- … and 2 more centers
Australia · 9 centers
- AU-Adelaide-FLINDERS — Adelaide
- AU-Adelaide-RAH — Adelaide
- AU-Birtinya-SUNSHINECOAST — Birtinya
- AU-Brisbane-PAH — Brisbane
- AU-Camperdown-RPA — Camperdown
- AU-Melbourne-AUSTIN — Melbourne
- AU-Melbourne-MONASH — Melbourne
- AU-Melbourne-PMCC — Melbourne
- … and 1 more center
United States · 8 centers
- US-San Francisco CA-UCSF — San Francisco
- US-Orlando FL-ORLANDOHEALTH — Orlando
- US-Atlanta GA-EMORY — Atlanta
- US-Chigago IL-UHCHICAGO — Chicago
- US-Kansas City KS-KUMC — Kansas City
- US-Baltimore MD-UMGCCC — Baltimore
- US-St Louis MO-WASHU — St Louis
- US-Cincinnati OH-CINCY — Cincinnati
Japan · 4 centers
- JP-Chuo-Ku-CHIBA — Chūōku
- JP-Nagasaki Shi-NAGASAKI — Nagasaki
- JP-Nishi-Gun-YAMAGATA — Yamagata
- JP-Yoshida-Gun-FUKUI — Yoshida
Estonia · 2 centers
- EE-Tallinn-REGIONAALHAIGLA — Tallinn
- EE-Tartu-TARTU — Tartu
Finland · 2 centers
- FI-Oulu-OYS — Oulu
- FI-Tampere-TAYS — Tampere
Sweden · 1 center
- SE-Lund-Suh — Lund
Identifiers
NCT: NCT07223814 · HOVON 181 AML · 2025-522767-15-00