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

NCT05453903 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR10912475276617ALE10022021-003999-142023-506582-58-00
• Study Type: interventional
• Target: 196
• Locations: 8 countries
• Sites: 32

Brief 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).

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 3 Years 3 months

• 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.

  Up to 3 Years 3 months

• 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.

  End of Cycle 1 (28 days)

Secondary Outcomes (6)

• Plasma Concentration of Bleximenib

  Up to 3 Years 3 months

• Number of Participants with Depletion of Leukemic Blasts

  Up to 3 Years 3 months

• Percentage of Participants who Achieve Complete Remission (CR)

  Up to 3 Years 3 months

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

  Up to 3 Years 3 months

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

  Up to 3 Years 3 months

Study Arms (3)

Arm A: Relapsed/Refractory Setting

EXPERIMENTAL

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).

Drug: Bleximenib; Drug: Venetoclax (VEN); Drug: Azacitidine (AZA)

Arm B: Newly Diagnosed Chemotherapy Ineligible Setting

EXPERIMENTAL

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.

Drug: Bleximenib; Drug: Venetoclax (VEN); Drug: Azacitidine (AZA)

Arm C: Newly Diagnosed Chemotherapy Eligible Setting

EXPERIMENTAL

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.

Drug: Bleximenib; Drug: Cytarabine; Drug: Daunorubicin or Idarubicin

Interventions

Daunorubicin or Idarubicin DRUG

Participants will receive daunorubicin or idarubicin.

Arm C: Newly Diagnosed Chemotherapy Eligible Setting

Cytarabine DRUG

Participants will receive cytarabine.

Arm C: Newly Diagnosed Chemotherapy Eligible Setting

Bleximenib DRUG

Participants will receive bleximenib.

Also known as: JNJ-75276617

Arm A: Relapsed/Refractory Setting; Arm B: Newly Diagnosed Chemotherapy Ineligible Setting; Arm C: Newly Diagnosed Chemotherapy Eligible Setting

Venetoclax (VEN) DRUG

Participants will receive VEN.

Arm A: Relapsed/Refractory Setting; Arm B: Newly Diagnosed Chemotherapy Ineligible Setting

Azacitidine (AZA) DRUG

Participants will receive AZA.

Arm A: Relapsed/Refractory Setting; Arm B: Newly Diagnosed Chemotherapy Ineligible Setting

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (32)

The University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Albert Einstein College Of Medicine

New York, New York, 10461, United States

Location

Novant Health

Charlotte, North Carolina, 28204, United States

Location

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Monash Medical Centre

Clayton, 3168, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G 1Z5, Canada

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Chu Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31100, France

Location

CHU de Tours - Hôpital de Bretonneau

Tours, 37044, France

Location

Charite Universitaetsmedizin Berlin

Berlin, 13353, Germany

Location

Universitatsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

Bologna, 40138, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

University College London Hospitals NHSFT

London, NW1 2PG, United Kingdom

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxfordshire, OX3 7LE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38905635 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine; Cytarabine; Daunorubicin; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2022
• First Posted: July 12, 2022
• Study Start: October 4, 2022
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): March 3, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); CA (1); DE (5); US (7); ES (5); FR (4); GB (3); IT (4)