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Leukemia, Myeloid, AcutePhase 1NCT05453903

A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies

A Phase 1 study testing Bleximenib, Venetoclax (VEN) and Azacitidine (AZA) in people with Leukemia, Myeloid, Acute, run by Janssen Research & Development, LLC at 32 sites in 8 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of bleximenib in combination with AML directed therapies (dose selection) and further to evaluate safety and tolerability of bleximenib in combination with AML directed therapies at the RP2D(s) (dose expansion). Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
Bleximenib, Venetoclax (VEN) and Azacitidine (AZA)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
196 participants
Where
32 sitesin 8 countries
Study dates
4 Oct 2022to 30 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Adolescent participants (defined as greater than or equal to [>=] 12 and less than [<] 18 years of age) are only eligible for the relapsed/refractory (R/R) cohort (Arm A, cohort A4)
  • Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo or secondary AML; b) relapsed/refractory (Arm A only); c) harboring KMT2A, NPM1, NUP98, or NUP214 alterations; d) Participants may receive emergency leukapheresis and/or cytarabine as cytoreductive therapy according to local practice guidelines
  • Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to (<=) 25*10^9 per liter (/L), adequate liver and renal function
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent participants only: Performance status >70 by Lansky scale (for participants <16 years of age) or >70 Karnofsky scale (for participants >16 years of age)
  • A female of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment
  • Must sign an informed consent form (ICF) indicating participant (or their legally authorized representative) understands the purpose of the study and procedures required for the study and is willing to participate in the study
  • Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Who cannot join

  • Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to WHO 2016 criteria
  • Leukemic involvement of the central nervous system
  • Recipient of solid organ transplant
  • Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or that was diagnosed within 6 months prior to the first dose of study treatment including, but not limited to: (a) Myocardial infarction; (b) Severe or unstable angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (<50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute neurologic events such as stroke or transient ischemic attack, intracranial or subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study treatment ;(g) Congestive heart failure (NYHA class III to IV); (h) Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for hypoalbuminemia)
  • Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapy that has not resolved to baseline or to grade 1 or less
  • Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation
  • Participants with diagnosis of Fanconi anemia, Kostmann syndrome, Shwachman diamond syndrome, or any other known bone marrow failure syndrome

Trial locations and contacts

32 sites in 8 countries.

32 sites in 8 countries

United States7 sites

  • The University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Novant Health

    Charlotte, North Carolina, 28204

  • City of Hope

    Duarte, California, 91010

  • MD Anderson

    Houston, Texas, 77030

  • Albert Einstein College Of Medicine

    New York, New York, 10461

  • Novant Health Forsyth Medical Center

    Winston-Salem, North Carolina, 27103

Other trials in United States

Germany5 sites

  • Charite Universitaetsmedizin Berlin

    Berlin, 13353

  • Universitatsklinikum Carl Gustav Carus Dresden

    Dresden, 01307

  • Universitaetsklinikum Heidelberg

    Heidelberg, 69120

  • Universitaetsklinikum Leipzig

    Leipzig, 04103

  • Universitatsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Spain5 sites

  • Hosp Clinic de Barcelona

    Barcelona, 08036

  • Hosp. de La Santa Creu I Sant Pau

    Barcelona, 08041

  • Hosp Univ Vall D Hebron

    Barcelona, 8035

  • Hosp Univ Fund Jimenez Diaz

    Madrid, 28040

  • Clinica Univ. de Navarra

    Pamplona, 31008

Other trials in Spain

France4 sites

  • Institut Paoli Calmettes

    Marseille, 13273

  • Chu Rennes Hopital Pontchaillou

    Rennes, 35033

  • Institut Universitaire du Cancer Toulouse Oncopole

    Toulouse, 31100

  • CHU de Tours - Hôpital de Bretonneau

    Tours, 37044

Other trials in France

Italy4 sites

  • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

    Bologna, 40138

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola, 47014

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, 20162

  • IRCCS Istituto Clinico Humanitas

    Rozzano, 20089

Other trials in Italy

Australia3 sites

  • Monash Medical Centre

    Clayton, 3168

  • Peter MacCallum Cancer Centre

    Melbourne, 3000

  • Westmead Hospital

    Westmead, 2145

Other trials in Australia

United Kingdom3 sites

  • University College London Hospitals NHSFT

    London, NW1 2PG

  • Christie Hospital NHS Trust

    Manchester, M20 4BX

  • Oxford University Hospitals NHS Trust

    Oxfordshire, OX3 7LE

Other trials in United Kingdom

Canada1 site

  • Princess Margaret Cancer Centre University Health Network

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

About this study

Official title: A Phase 1b Study of Bleximenib in Combination With AML-Directed Therapies for Participants With Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of bleximenib in combination with AML directed therapies (dose selection) and further to evaluate safety and tolerability of bleximenib in combination with AML directed therapies at the RP2D(s) (dose expansion).

Being tested
Bleximenib, Venetoclax (VEN), Azacitidine (AZA), Cytarabine, Daunorubicin or Idarubicin
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

    Also called JNJ-75276617

    Participants will receive bleximenib.

  • Venetoclax (VEN)Drug

    Participants will receive VEN.

  • Azacitidine (AZA)Drug

    Participants will receive AZA.

  • CytarabineDrug

    Participants will receive cytarabine.

  • Daunorubicin or IdarubicinDrug

    Participants will receive daunorubicin or idarubicin.

Study groups in NCT05453903
Study groupRoleWhat they receive
Arm A: Relapsed/Refractory SettingExperimentalParticipants with relapsed/refractory AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations will receive bleximenib in combination with either venetoclax (VEN) (Cohort A1: bleximenib+VEN) or azacitidine (AZA) (Cohort A2: bleximenib +AZA) or VEN+AZA (Cohort A3: bleximenib+VEN+AZA) or VEN + AZA (Cohort A4: bleximenib + VEN + AZA) in adolescent participants aged greater than or equal to (>=) 12 years and less than (<) 18 years of age, to select the recommended phase 2 dose (RP2D) of bleximenib in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive bleximenib in combination with AML directed therapies at the RP2D(s).
Receives: Drug: Bleximenib; Drug: Venetoclax (VEN); Drug: Azacitidine (AZA)
Arm B: Newly Diagnosed Chemotherapy Ineligible SettingExperimentalParticipants will receive bleximenib in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring KMT2A, NPM1, NUP98, or NUP214 alterations who are >=75 years of age or >=18 years of age to <75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.
Receives: Drug: Bleximenib; Drug: Venetoclax (VEN); Drug: Azacitidine (AZA)
Arm C: Newly Diagnosed Chemotherapy Eligible SettingExperimentalParticipants will receive combination of bleximenib with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants >= 18 to <75 years of age with AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations and eligible for intensive chemotherapy.
Receives: Drug: Bleximenib; Drug: Cytarabine; Drug: Daunorubicin or Idarubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Adverse Events (AEs)

    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

    Measured: Up to 3 Years 3 months

  2. Number of Participants with Adverse Events (AEs) by Severity

    Number of Participants with AEs by severity will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

    Measured: Up to 3 Years 3 months

  3. Number of Participants with Dose-limiting Toxicity (DLT)

    Number of participants with DLT will be reported according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

    Measured: End of Cycle 1 (28 days)

Secondary outcomes (6)

  1. Plasma Concentration of Bleximenib

    Plasma samples will be analyzed to determine concentrations of bleximenib using a validated, specific, and sensitive method.

    Measured: Up to 3 Years 3 months

  2. Number of Participants with Depletion of Leukemic Blasts

    Number of participants with depletion of leukemic blasts will be reported.

    Measured: Up to 3 Years 3 months

  3. Percentage of Participants who Achieve Complete Remission (CR)

    Percentage of participants who achieve complete Remission (CR) will be reported. CR is defined as Bone marrow blasts less than (<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (>=) 1.0*10^9/Liter (L) (1,000/microliter [mcL]); Platelet count >= 100 * 10^9/L (100,000/mcL).

    Measured: Up to 3 Years 3 months

  4. Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh)

    Percentage of participants who achieve complete remission with partial hematologic recovery (CRh) will be reported. CRh is defined as All criteria of CR with both ANC >0.5 * 10^9/L (500/mcL) and platelet count >50 * 10^9/L (50,000/mcL).

    Measured: Up to 3 Years 3 months

  5. Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi)

    Percentage of participants who achieve complete remission with incomplete hematologic recovery (CRi) will be reported. CRi is defined as All CR criteria except for residual neutropenia (<1.0*10^9/L [1,000/mcL]) or thrombocytopenia (<100 * 10^9/L [100,000/mcL]).

    Measured: Up to 3 Years 3 months

  6. Percentage of Participants who Achieved Overall Response

    Percentage of participants who achieve overall response will be reported. Overall response rate (ORR) is defined as the percentage of participants achieving CR, CRh, or CRi, morphologic leukemia-free state (MLFS) or partial remission (PR).

    Measured: Up to 3 Years 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2022
  2. Study start4 Oct 2022
  3. Primary completion30 Oct 2026 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
196 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05453903
Sponsor's protocol ID
CR109124
Other IDs
75276617ALE1002, 2021-003999-14, 2023-506582-58-00, 2023
Status last verified
Sep 2026
First submitted
8 Jul 2022
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of Johnson \& Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Publications

  • Kwon MC, Thuring JW, Querolle O, Dai X, Verhulst T, Pande V, Marien A, Goffin D, Wenge DV, Yue H, Cutler JA, Jin C, Perner F, Hogeling SM, Shaffer PL, Jacobs F, Vinken P, Cai W, Keersmaekers V, Eyassu F, Bhogal B, Verstraeten K, El Ashkar S, Perry JA, Jayaguru P, Barreyro L, Kuchnio A, Darville N, Krosky D, Urbanietz G, Verbist B, Edwards JP, Cowley GS, Kirkpatrick R, Steele R, Ferrante L, Guttke C, Daskalakis N, Pietsch EC, Wilson DM, Attar R, Elsayed Y, Fischer ES, Schuringa JJ, Armstrong SA, Packman K, Philippar U. Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias. Blood. 2024 Sep 12;144(11):1206-1220. doi: 10.1182/blood.2023022480.

    PubMed 38905635

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bleximenib, Venetoclax (VEN) and Azacitidine (AZA) in people with Leukemia, Myeloid, Acute, run by Janssen Research & Development, LLC at 32 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Germany, Spain, France, Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Adverse Events (AEs) (time frame: Up to 3 Years 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05453903, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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Clinical Trial NCT05453903 | AzTrials