Clinical trial NCT05453903: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-07-12
Enrollment: 200
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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 outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 3 Years 3 months
measure: Number of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 3 Years 3 months
measure: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: End of Cycle 1 (28 days)
Secondary outcomes:
measure: Plasma Concentration of Bleximenib
timeFrame: Up to 3 Years 3 months
measure: Number of Participants with Depletion of Leukemic Blasts
timeFrame: Up to 3 Years 3 months
measure: Percentage of Participants who Achieve Complete Remission (CR)
timeFrame: Up to 3 Years 3 months
measure: Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh)
timeFrame: Up to 3 Years 3 months
measure: Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi)
timeFrame: Up to 3 Years 3 months
measure: Percentage of Participants who Achieved Overall Response
timeFrame: Up to 3 Years 3 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Albert Einstein College Of Medicine
state: New York
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Westmead
country: Australia
facility: Westmead Hospital
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Rennes Cedex 9
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Tours
country: France
facility: CHU de Tours - Hôpital de Bretonneau
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus Dresden
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Bologna
country: Italy
facility: Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: London
country: United Kingdom
facility: University College London Hospitals NHSFT
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Oxfordshire
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: