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

NCT05453903
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Phase
Phase 1
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Recruitment status
Active, not recruiting
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Participants
196
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Lead sponsor
Janssen Research & Development, LLC
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Start date
2022-10-04
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Number of sites
32
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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).
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Short title
A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-03-03
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First posted
2022-07-12
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Registry last updated
2026-08-28
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Primary completion date
2026-10-30
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Start date
2022-10-04
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Actual participants
196
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Participants
196
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Participant count basis
Actual
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Protocol amendments
6
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Number of sites
32
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Janssen Research & Development, LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05453903
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ClinicalTrials.gov ID
NCT05453903
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Number of Participants with Adverse Events (AEs)

    Timeframe: 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

    Timeframe: 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)

    Timeframe: 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.

  1. Plasma Concentration of Bleximenib

    Timeframe: 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

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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

    Timeframe: 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).

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children, Adults, Older adults
Minimum age
12 Years
Healthy volunteers
No

  • 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

  • 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
Sources for eligibility
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  • The University of Alabama at BirminghamBirmingham, United States
  • City of HopeDuarte, United States
  • Massachusetts General HospitalBoston, United States
  • Albert Einstein College Of MedicineNew York, United States
  • Novant HealthCharlotte, United States
  • Novant Health Forsyth Medical CenterWinston-Salem, United States
  • MD AndersonHouston, United States
  • Monash Medical CentreClayton, Australia
  • Peter MacCallum Cancer CentreMelbourne, Australia
  • Westmead HospitalWestmead, Australia
  • Princess Margaret Cancer Centre University Health NetworkToronto, Canada
  • Institut Paoli CalmettesMarseille, France
  • Chu Rennes Hopital PontchaillouRennes, France
  • Institut Universitaire du Cancer Toulouse OncopoleToulouse, France
  • CHU de Tours - Hôpital de BretonneauTours, France
  • Charite Universitaetsmedizin BerlinBerlin, Germany
  • Universitatsklinikum Carl Gustav Carus DresdenDresden, Germany
  • Universitaetsklinikum HeidelbergHeidelberg, Germany
  • Universitaetsklinikum LeipzigLeipzig, Germany
  • Universitatsklinikum UlmUlm, Germany
  • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di BolognaBologna, Italy
  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriMeldola, Italy
  • ASST Grande Ospedale Metropolitano NiguardaMilan, Italy
  • IRCCS Istituto Clinico HumanitasRozzano, Italy
  • Hosp Clinic de BarcelonaBarcelona, Spain

And 7 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-506582-58-00
  • 2021-003999-14
  • 75276617ALE1002
Sources for references
clinicaltrials.gov

Related records

Drugs (5)

Lead sponsors (1)

Conditions (1)

Targets (4)