BleximenibVenetoclax (VEN)Azacitidine (AZA)CytarabineDaunorubicin or Idarubicin
Bleximenib: Participants will receive bleximenib.
Venetoclax (VEN): Participants will receive VEN.
Azacitidine (AZA): Participants will receive AZA.
Cytarabine: Participants will receive cytarabine.
Daunorubicin or Idarubicin: Participants will receive daunorubicin or idarubicin.
Study 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).
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Number of Participants with Adverse Events (AEs) — 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.
Number of Participants with Adverse Events (AEs) by Severity — 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.
Number of Participants with Dose-limiting Toxicity (DLT) — 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.
Trial sites (32)
Facility
City
Region
Status
The University of Alabama at Birmingham
Birmingham
Alabama
City of Hope
Duarte
California
Massachusetts General Hospital
Boston
Massachusetts
Albert Einstein College Of Medicine
New York
New York
Novant Health
Charlotte
North Carolina
Novant Health Forsyth Medical Center
Winston-Salem
North Carolina
MD Anderson
Houston
Texas
Monash Medical Centre
Clayton
Australia
Peter MacCallum Cancer Centre
Melbourne
Australia
Westmead Hospital
Westmead
Australia
Princess Margaret Cancer Centre University Health Network
Toronto
Ontario
Institut Paoli Calmettes
Marseille
France
Chu Rennes Hopital Pontchaillou
Rennes
France
Institut Universitaire du Cancer Toulouse Oncopole
Toulouse
France
CHU de Tours - Hôpital de Bretonneau
Tours
France
Charite Universitaetsmedizin Berlin
Berlin
Germany
Universitatsklinikum Carl Gustav Carus Dresden
Dresden
Germany
Universitaetsklinikum Heidelberg
Heidelberg
Germany
Universitaetsklinikum Leipzig
Leipzig
Germany
Universitatsklinikum Ulm
Ulm
Germany
Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
Bologna
Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola
Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan
Italy
IRCCS Istituto Clinico Humanitas
Rozzano
Italy
Hosp Clinic de Barcelona
Barcelona
Spain
Hosp. de La Santa Creu I Sant Pau
Barcelona
Spain
Hosp Univ Vall D Hebron
Barcelona
Spain
Hosp Univ Fund Jimenez Diaz
Madrid
Spain
Clinica Univ. de Navarra
Pamplona
Spain
University College London Hospitals NHSFT
London
United Kingdom
Christie Hospital NHS Trust
Manchester
United Kingdom
Oxford University Hospitals NHS Trust
Oxfordshire
United Kingdom
More Janssen Research & Development, LLC trials in the UK
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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