The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) of bleximenib in phase 1 Part 1 (Dose Escalation) and to determine the safety and tolerability at RP2D in Phase 1 Part 2 (Dose expansion). The purpose of the Phase 2 part of the study is to evaluate the efficacy of bleximenib at the RP2D.
Eligibility
Sex
ALL
Min age
2 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
Phase 1:
* Age 2 years to less than (\<) 18 years of age (pediatric cohort only), all other cohorts 18 years and above
* Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options
* Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A), nucleophosmin 1 gene (NPM1) or nucleoporin 98 gene or nucleoporin 214 gene (NUP98 or NUP214) alterations
Phase: 2
* Participants greater than 18 years are eligible
* Must have had an initial diagnosis of acute myeloid leukemia (AML) per the WHO 2022 classification criteria and have relapsed/refractory disease
* AML harboring KMT2A-r (gene rearrangement/translocation) or NPM1 mutations only
For Both Phase 1 and 2:
* Pretreatment clinical laboratory values meeting the following criteria: (a) Hematology: white blood cell (WBC) count \<= 20\*10\^9/liter (L) and (b) renal function; For adult participants, estimated or measured glomerular filtration rate \>= 30 milliliter per minute (mL/min) per four variable MDRD equation. For pediatric participants an estimated or measured glomerular filtration rate \>=40 mL/min per the CKiD (Chronic Kidney Disease in Children) Schwartz formula
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Pediatric 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
* Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment
Exclusion Criteria:
* Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to World Health Organization (WHO) 2016 criteria
* Active central nervous system (CNS) disease
* Prior solid organ transplantation
* QTc according to Fridericia's formula (QTcF) for males \>= 450 millisecond (msec) or for females \>= 470 msec. Participants with a family history of Long QT syndrome are excluded
* Exclusion criteria related to stem cell transplant: a. Received prior treatment with allogenic bone marrow or stem cell transplant \<=3 months before the first dose of study treatment ; b. Has evidence of graft versus host disease; c. Received donor lymphocyte infusion \<=1 month before the first dose of study treatment; d. Requires immunosuppressant therapy (exception: daily doses \<=10 milligrams (mg) prednisone or equivalent are allowed for adrenal replacement)
* Prior cancer immunotherapy within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment. Additional prior cancer therapies must not be given within 4 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter)
Primary outcome measure(s)
Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability — Up to 4 years and 9 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.
Phase 1: Number of Participants with AEs by Severity — Up to 4 years and 9 months 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.
Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT) — Up to 28 days Cycle 1 Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.
Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh) — Up to 4 years and 9 months Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment.
Trial sites (102)
Facility
City
Region
Status
City of Hope
Duarte
California
Recruiting
University of California Irvine Medical Center
Orange
California
Completed
University of California San Francisco
San Francisco
California
Recruiting
UCSF Benioff Children's Hospital
San Francisco
California
Recruiting
University of Chicago
Chicago
Illinois
Recruiting
St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation
Indianapolis
Indiana
Recruiting
Norton Cancer Institute
Louisville
Kentucky
Completed
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Recruiting
Karmanos Cancer Institute
Detroit
Michigan
Completed
Start Midwest
Grand Rapids
Michigan
Recruiting
University of New Mexico
Albuquerque
New Mexico
Recruiting
Roswell Park Comprehensive Cancer Center
Buffalo
New York
Recruiting
NYU Langone Medical Center
New York
New York
Recruiting
Montefiore Medical Center
The Bronx
New York
Recruiting
Oregon Health And Science University
Portland
Oregon
Recruiting
Fox Chase Cancer Center
Philadelphia
Pennsylvania
Completed
Maine Health
Providence
Rhode Island
Recruiting
University of Tennessee Medical Center
Knoxville
Tennessee
Recruiting
Baylor University Medical Center
Dallas
Texas
Recruiting
Houston Methodist Hospital
Houston
Texas
Recruiting
MD Anderson
Houston
Texas
Recruiting
San Antonio Methodist TX Transplant Physicians Group
San Antonio
Texas
Recruiting
Virginia Commonwealth University
Richmond
Virginia
Recruiting
Swedish Cancer Institute
Seattle
Washington
Recruiting
Medical College of WI at Froedtert
Milwaukee
Wisconsin
Recruiting
Monash Medical Centre
Clayton
Australia
Recruiting
Royal Perth Hospital
Perth
Australia
Recruiting
Gold Coast University Hospital
Southport
Australia
Recruiting
Ghent University Hospital
Ghent
Belgium
Recruiting
IDOR - Regional Brasilia
Brasília
Brazil
Recruiting
Liga Norte Riograndense Contra O Cancer
Natal
Brazil
Recruiting
Ministerio da Saude Instituto Nacional do Cancer
Rio de Janeiro
Brazil
Recruiting
Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
São Paulo
Brazil
Recruiting
IDOR - Regional Sao Paulo
São Paulo
Brazil
Recruiting
Fundacao Antonio Prudente A C Camargo Cancer Center
São Paulo
Brazil
Recruiting
Vancouver Coastal Health
Vancouver
British Columbia
Recruiting
Princess Margaret Cancer Centre University Health Network
Toronto
Ontario
Recruiting
Hopital Maisonneuve Rosemont
Montreal
Quebec
Recruiting
Peking University First Hospital
Beijing
China
Recruiting
+ 62 more sites — see the full list on the official registry below.
Official registry record
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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