Acute Myeloid LeukemiaPhase 3NCT07223814
Bleximenib in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for Treatment of Patients With Acute Myeloid Leukemia (AML)
A Phase 3 study testing Bleximenib, Cytarabine and Daunorubicin or Idarubicin in people with Acute Myeloid Leukemia, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 98 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Bleximenib, Cytarabine and Daunorubicin or Idarubicin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 875 participants
- Where
- 98 sitesin 13 countries
- Study dates
- 1 Mar 2026to Dec 2033
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
98 sites in 13 countries. Contact the study team or a site near you to ask about taking part.
98 sites in 13 countries
Netherlands18 sites, 18 recruiting
- Recruiting
NL-Den Bosch-JBZ
's-Hertogenbosch
A. Herbers
- Recruiting
NL-Amersfoort-MEANDERMC
Amersfoort
M.F. Corsten
- Recruiting
NL-Amsterdam-AMSTERDAMUMC
Amsterdam
D.C. de Leeuw
- Recruiting
NL-Amsterdam-OLVG
Amsterdam
H. Mooij
- Recruiting
NL-Arnhem-RIJNSTATE
Arnhem
M. Cuipers
- Recruiting
NL-Breda-AMPHIA
Breda
R. Fiets
- Recruiting
NL-Dordrecht-ASZ
Dordrecht
P. Westerweel
- Recruiting
NL-Eindhoven-MAXIMAMC
Eindhoven
L. Tick
- Recruiting
NL-Groningen-UMCG
Groningen
G. Huls
- Recruiting
NL-Leeuwarden-FRISIUSMC
Leeuwarden
B. Franken
- Recruiting
NL-Leiden-LUMC
Leiden
J.H. Veelken
- Recruiting
NL-Maastricht-MUMC
Maastricht
C.H.M.J. van Elssen
- Recruiting
NL-Nieuwegein-ANTONIUS
Nieuwegein
M. Söhne
- Recruiting
NL-Nijmegen-RADBOUD
Nijmegen
F. in 't Hout
- Recruiting
NL-Rotterdam-ERASMUCMC
Rotterdam
M.H.G. Raaijmakers
- Recruiting
NL-Den Haag-HAGA
The Hague
D. Lammeren, van-Venema
- Recruiting
NL-Utrecht-UMCUTRECHT
Utrecht
L. van Hussen-Daenen
- Recruiting
NL-Zwolle-ISALA
Zwolle
T. de Waal
Germany15 sites, 15 recruiting
- Recruiting
DE-Aachen-UKAACHEN
Aachen
M. Chrysandt
- Recruiting
DE-Bochum-RUB
Bochum
R. Schroers
- Recruiting
DE-Bonn-UNIBONN
Bonn
L. Teichmann
- Recruiting
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
Braunschweig
C. Schünemann
- Recruiting
DE-Greifswald-UNIGREIFSWALD
Greifswald
J. Krönke
- Recruiting
DE-Halle-UMH
Halle
M. Heuser
- Recruiting
DE-Hamburg-ASKLEPIOSSTGEORG
Hamburg
A. Elmaagacli
- Recruiting
DE-Hannover-MHHANNOVER
Hanover
F. Thol
- Recruiting
DE-Heilbronn-SLK
Heilbronn
M. Lindauer
- Recruiting
DE-Homburg-UNIKLINIKSAARLAND
Homburg
J. Bittenbring
- Recruiting
DE-Karlsruhe-KLINIKUMKARLSRUHE
Karlsruhe
M. Ringhoffer
- Recruiting
DE-Oldenburg-KLINIKUMOLDENBURG
Oldenburg
A. Voß
- Recruiting
DE-Passau-KLINIKUMPASSAU
Passau
T. Suedhoff
- Recruiting
DE-Rostock-MUROSTOCK
Rostock
F. Theis
- Recruiting
DE-Ulm-UNIKLINKULM
Ulm
H. Döhner
Belgium14 sites, 14 recruiting
- Recruiting
BE-Antwerpen-UZA
Antwerp
E. de Backer
- Recruiting
BE-Antwerpen-ZAS
Antwerp
D. Breems
- Recruiting
BE-Brugge-AZBRUGGE
Bruges
T. Lodewyck
- Recruiting
BE-Brussel-BORDET
Brussels
S. Wittnebel
- Recruiting
BE-Bruxelles-STLUC
Brussels
M.C. Vekemans
- Recruiting
Be-Charleroi-GHDC
Charleroi
V. Robin
- Recruiting
BE-Geel-STDIMPNA
Geel
U. Douven
- Recruiting
BE-Gent-UZGENT
Ghent
T. De Corte
- Recruiting
BE-Hasselt-VIRGAJESSE (Jessa Ziekenhuis)
Hasselt
L. Lammertijn
- Recruiting
BE-Haine-Saint-Paul-JOLIMONT
Jolimont
R. Lattenist
- Recruiting
BE-Leuven-UZLEUVEN
Leuven
J. Maertens
- Recruiting
BE-Liege-CHULIEGE
Liège
A. De Voeght
- Recruiting
BE-Liege-MONTLEGIA
Liège
Q. Perlot
- Recruiting
BE-Yvoir-MONTGODINNE
Yvoir
E. Collinge
United States13 sites, 13 recruiting
- Recruiting
US-Atlanta GA-EMORY
Atlanta, Georgia, 30322
W. Blum
- Recruiting
US-Baltimore MD-UMGCCC
Baltimore, Maryland, 21201
M. Baer
- Recruiting
US-Charlotte NC-NOVANTCHARLOTTE
Charlotte, North Carolina, 28204
J. Dugan
- Recruiting
US-Chigago IL-UHCHICAGO
Chicago, Illinois, 60637
W. Stock
- Recruiting
US-Cincinnati OH-CINCY
Cincinnati, Ohio, 45219
E. Curran
- Recruiting
US-Colombus OH-OSU
Columbus, Ohio, 43210
S. Handa
- Recruiting
US-Kansas City KS-KUMC
Kansas City, Kansas, 66103
T. Lin
- Recruiting
US-Los Angeles CA-UCLA
Los Angeles, California, 90095
G. Schiller
- Recruiting
US-Orlando FL-ORLANDOHEALTH
Orlando, Florida, 32806
J. Varela
- Recruiting
US-Pittsburgh PA-PITT
Pittsburgh, Pennsylvania, 15260
A. Im
- Recruiting
US-San Francisco CA-UCSF
San Francisco, California, 94115
R. Olin
- Recruiting
US-St Louis MO-WASHU
St Louis, Missouri, 63110
G. Uy
- Recruiting
US-Winston-Salem NC-NOVANTWINSTON
Winston-Salem, North Carolina, 27103
J. Dugan
Australia11 sites, 11 recruiting
- Recruiting
AU-Adelaide-FLINDERS
Adelaide
A. Beligaswatte
- Recruiting
AU-Adelaide-RAH
Adelaide
D. Hiwase
- Recruiting
AU-Birtinya-SUNSHINECOAST
Birtinya
J. Conn
- Recruiting
AU-Brisbane-PAH
Brisbane
M. Harwood
- Recruiting
AU-Brisbane-RBWH
Brisbane
C. McNamara
- Recruiting
AU-Camperdown-RPA
Camperdown
D. Mc Culloch
- Recruiting
AU-Melbourne-AUSTIN
Melbourne
C.Y. Fong
- Recruiting
AU-Melbourne-MONASH
Melbourne
C.C. Chua
- Recruiting
AU-Melbourne-PMCC
Melbourne
A. Wei
- Recruiting
AU-Sydney-RNSH
Sydney
J. Othman
- Recruiting
AU-Sydney-WSAH
Sydney
L. Vaughan
Japan6 sites, 6 recruiting
- Recruiting
JP-Chuo-Ku-CHIBA
Chūōku
E. Sakaida
- Recruiting
JP-Maebashi-Shi-GUNMA
Maebashi
S. Takada
- Recruiting
JP-Nagasaki Shi-NAGASAKI
Nagasaki
K. Ando
- Recruiting
JP-Nagoya-shi-JRC
Nagoya
T. Goto
- Recruiting
JP-Nishi-Gun-YAMAGATA
Yamagata
H. Yokoyama
- Recruiting
JP-Yoshida-Gun-FUKUI
Yoshida
T. Yamauchi
Finland5 sites, 5 recruiting
- Recruiting
FI-Helsinki-HUS
Helsinki
M. Kontro
- Recruiting
FI-Kuopio-KYS
Kuopio
A. Turunen
- Recruiting
FI-Oulu-OYS
Oulu
K. Launonen
- Recruiting
FI-Tampere-TAYS
Tampere
J. Rimpiläinen
- Recruiting
FI-Turku-TYKS
Turku
P. Ettala
Switzerland5 sites, 5 recruiting
- Recruiting
CH-Bern-INSEL
Bern
T. Pabst
- Recruiting
CH-Fribourg-HFR
Fribourg
A. Efthymiou
- Recruiting
CH-Geneve (14)-HCUGE
Geneva
Y. Beaeuverd
- Recruiting
CH-St. Gallen-KSSG
Sankt Gallen
M. Schittenhelm
- Recruiting
CH-Zürich-USZ
Zurich
A. Theocharides
Spain4 sites, 4 recruiting
- Recruiting
ES-Barcelona-MUTUATERRASSA
Barcelona
F. Vall-Llovera Calmet
- Recruiting
ES-Lleida-ICSVILANOVA
Lleida
A. Garcia Guinon
- Recruiting
ES-Palma-HSLL
Palma de Mallorca
A. Cladera Serra
- Recruiting
ES-Palma-SSIB
Palma de Mallorca
A. Sampol
Norway3 sites, 3 recruiting
- Recruiting
NO-Bergen-HELSEBERGEN
Bergen
B.J. Gjertsen
- Recruiting
NO-Oslo-OSLOUH
Oslo
A. Lenartova
- Recruiting
NO-Trondheim-STOLAV
Trondheim
A.S. von Krogh
Estonia2 sites, 2 recruiting
- Recruiting
EE-Tallinn-REGIONAALHAIGLA
Tallinn
K. Palk
- Recruiting
EE-Tartu-TARTU
Tartu
A. Kaare
Austria1 site, 1 recruiting
- Recruiting
AT-Linz-ORDENSKLINIKUM
Linz
S. Machherndl-Spandl
About this study
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
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.
Read more
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
- Being tested
- Bleximenib, Cytarabine, Daunorubicin or Idarubicin, Placebo
- Keywords
- AML, adult, newly diagnosed AML, NPM1, KMT2A
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BleximenibDrug
Participants will receive bleximenib
CytarabineDrug
Participants will receive Cytarabine
Daunorubicin or IdarubicinDrug
Participants will receive Daunorubicin or Idarubicin
PlaceboDrug
Participants will receive Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: Drug: Cytarabine; Drug: Daunorubicin or Idarubicin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
Defined as the proportion of participants achieving a given response after induction cycle 1 and after induction cycle 2.
Measured: 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
Defined as the time from achieving first response of CR to hematologic relapse or death from any cause, whichever occurs first.
Measured: 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
To assess the percentage of participants undergoing an allo-SCT as part of protocol treatment
Measured: Up to 7 years and 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2025
- Study start1 Mar 2026
- Primary completionJun 2030 (estimated)
- Study completionDec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 875 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen Nederland
- Sponsor type
- University, hospital or other
- Collaborators
- German-Austrian Acute Myeloid Leukemia Study Group
- Responsible party
- Sponsor
- Investigators
- M.H.G.P. Raaijmakers, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07223814
- Sponsor's protocol ID
- HOVON 181 AML
- Other IDs
- 2025-522767-15-00, 2025
- Status last verified
- Oct 2026
- First submitted
- 30 Oct 2025
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the current publication policy the protocol and Statistica! Analysis Plan ( SAP) will be shared. The principal lnvestigators can be contacted for IPD sharing after the publication of the study results. According to 'HOVON sample and/or Data request Form' theHOVON director; chair of theHOVON Acute Myeloid Leukemie working group, the study PI and Coordinating lnvestigator should approve data/sample sharing.