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NCT Number: NCT05453903

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

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).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Monash Medical Centre, Clayton, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Bleximenib

Drug

Participants will receive bleximenib.

Other names: JNJ-75276617

Venetoclax (VEN)

Drug

Participants will receive VEN.

Azacitidine (AZA)

Drug

Participants will receive AZA.

Cytarabine

Drug

Participants will receive cytarabine.

Daunorubicin or Idarubicin

Drug

Participants will receive daunorubicin or idarubicin.

Primary outcomes

  1. Number of Participants with Adverse Events (AEs)

    Time frame: Up to 3 Years 3 months

    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.

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

    Time frame: Up to 3 Years 3 months

    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.

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

    Time frame: End of Cycle 1 (28 days)

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

Secondary outcomes

  1. Plasma Concentration of Bleximenib

    Time frame: Up to 3 Years 3 months

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

  2. Number of Participants with Depletion of Leukemic Blasts

    Time frame: Up to 3 Years 3 months

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

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

    Time frame: Up to 3 Years 3 months

    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).

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

    Time frame: Up to 3 Years 3 months

    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).

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

    Time frame: Up to 3 Years 3 months

    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]).

  6. Percentage of Participants who Achieved Overall Response

    Time frame: Up to 3 Years 3 months

    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).

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Jul 12, 2022
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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