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

NCT ID: NCT05453903

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-04

Study Completion Date

2027-03-19

Brief Summary

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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).

Detailed Description

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Conditions

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Leukemia, Myeloid, Acute

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Relapsed/Refractory Setting

Participants 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).

Group Type EXPERIMENTAL

Bleximenib

Intervention Type DRUG

Participants will receive bleximenib.

Venetoclax (VEN)

Intervention Type DRUG

Participants will receive VEN.

Azacitidine (AZA)

Intervention Type DRUG

Participants will receive AZA.

Arm B: Newly Diagnosed Chemotherapy Ineligible Setting

Participants 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.

Group Type EXPERIMENTAL

Bleximenib

Intervention Type DRUG

Participants will receive bleximenib.

Venetoclax (VEN)

Intervention Type DRUG

Participants will receive VEN.

Azacitidine (AZA)

Intervention Type DRUG

Participants will receive AZA.

Arm C: Newly Diagnosed Chemotherapy Eligible Setting

Participants 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.

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.

Interventions

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Bleximenib

Participants will receive bleximenib.

Intervention Type DRUG

Venetoclax (VEN)

Participants will receive VEN.

Intervention Type DRUG

Azacitidine (AZA)

Participants will receive AZA.

Intervention Type DRUG

Cytarabine

Participants will receive cytarabine.

Intervention Type DRUG

Daunorubicin or Idarubicin

Participants will receive daunorubicin or idarubicin.

Intervention Type DRUG

Other Intervention Names

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JNJ-75276617

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status COMPLETED

City of Hope

Duarte, California, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Albert Einstein College Of Medicine

New York, New York, United States

Site Status RECRUITING

Novant Health

Charlotte, North Carolina, United States

Site Status RECRUITING

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States

Site Status RECRUITING

MD Anderson

Houston, Texas, United States

Site Status RECRUITING

Monash Medical Centre

Clayton, , Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status RECRUITING

Westmead Hospital

Westmead, , Australia

Site Status RECRUITING

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status ACTIVE_NOT_RECRUITING

Chu Rennes Hopital Pontchaillou

Rennes, , France

Site Status RECRUITING

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, , France

Site Status RECRUITING

CHU de Tours - Hôpital de Bretonneau

Tours, , France

Site Status RECRUITING

Charite Universitaetsmedizin Berlin

Berlin, , Germany

Site Status ACTIVE_NOT_RECRUITING

Universitatsklinikum Carl Gustav Carus Dresden

Dresden, , Germany

Site Status ACTIVE_NOT_RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Site Status ACTIVE_NOT_RECRUITING

Universitaetsklinikum Leipzig

Leipzig, , Germany

Site Status COMPLETED

Universitatsklinikum Ulm

Ulm, , Germany

Site Status ACTIVE_NOT_RECRUITING

Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

Bologna, , Italy

Site Status RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Site Status RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status RECRUITING

IRCCS Istituto Clinico Humanitas

Rozzano, , Italy

Site Status RECRUITING

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Hosp Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hosp Univ Vall D Hebron

Barcelona, , Spain

Site Status RECRUITING

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

Clinica Univ. de Navarra

Pamplona, , Spain

Site Status RECRUITING

University College London Hospitals NHSFT

London, , United Kingdom

Site Status RECRUITING

Christie Hospital NHS Trust

Manchester, , United Kingdom

Site Status RECRUITING

Oxford University Hospitals NHS Trust

Oxfordshire, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Australia Canada France Germany Italy Spain United Kingdom

Central Contacts

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Study Contact

Role: CONTACT

Phone: 844-434-4210

Email: [email protected]

References

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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.

Reference Type DERIVED
PMID: 38905635 (View on PubMed)

Other Identifiers

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75276617ALE1002

Identifier Type: OTHER

Identifier Source: secondary_id

2021-003999-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506582-58-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR109124

Identifier Type: -

Identifier Source: org_study_id