A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)
Phase 1/2 – combined early trial
Conditions:
Acute Leukemia
Sponsor: Janssen Research & Development, LLC
trial.available_in:
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Overview
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.
Who can participate
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)
Interventions
Bleximenib
DRUG
Locations
103
Australia (3)
Monash Medical Centre
Clayton
Royal Perth Hospital
Perth
Gold Coast University Hospital
Southport
Belgium (1)
Ghent University Hospital
Ghent
Brazil (6)
Instituto D Or de Pesquisa e Ensino
Brasília
Liga Norte Riograndense Contra O Cancer
Natal
Ministerio da Saude Instituto Nacional do Cancer
Rio de Janeiro
Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo
São Paulo
Instituto D Or de Pesquisa e Ensino IDOR
São Paulo
Fundacao Antonio Prudente A C Camargo Cancer Center
São Paulo
Canada (3)
Hopital Maisonneuve Rosemont
Montreal , Quebec
Princess Margaret Cancer Centre University Health Network
Toronto , Ontario
Vancouver Coastal Health
Vancouver , British Columbia
China (12)
Peking University First Hospital
Beijing
The First Hospital of Jilin University
Changchun
West China Hospital Si Chuan University
Chengdu
Nanfang Hospital of Southern Medical Hospital
Guangzhou
First Affiliated Hospital Medical School of Zhejiang University
Hangzhou
Qilu Hospital of Shandong University
Jinan
The First Affiliated Hospital of NanChang University
Nanchang
Zhongda Hospital Southeast University
Nanjing
Institute of Hematology and Blood Diseases Hospital
Tianjin
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
Wuhan
Henan Cancer Hospital
Zhengzhou
France (13)
Hopital Jean Minjoz
Besançon
Institut Paoli Calmettes
Marseille
CHU de Nantes hotel Dieu
Nantes
Hopital Saint Louis
Paris
Hopital trousseau- APHP
Paris
Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
Pessac
COMPLETED
CHU Lyon Sud
Pierre-Bénite
Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
Strasbourg
Institut Universitaire du Cancer Toulouse Oncopole
Toulouse
CHU Bretonneau
Tours
CHRU de Nancy - Hopitaux de Brabois
Vandœuvre-lès-Nancy
CHRU Nancy Brabois
Vandœuvre-lès-Nancy
Gustave Roussy
Villejuif
Israel (4)
Carmel Medical Center
Haifa
Hadassah University Hospita Ein Kerem
Jerusalem
Sheba Medical Center
Ramat Gan
Tel Aviv Sourasky Medical Center
Tel Aviv
Japan (11)
Kyushu University Hospital
Fukuoka
ACTIVE_NOT_RECRUITING
Fukushima Medical University Hospital
Fukushima
ACTIVE_NOT_RECRUITING
Kanazawa University Hospital
Kanazawa
ACTIVE_NOT_RECRUITING
National Cancer Center Hospital East
Kashiwa
ACTIVE_NOT_RECRUITING
Kobe City Medical Center General Hospital
Kobe
ACTIVE_NOT_RECRUITING
Gunmaken Saiseikai Maebashi Hospital
Maebashi
ACTIVE_NOT_RECRUITING
Nagoya University Hospital
Nagoya
COMPLETED
Hokkaido University Hospital
Sapporo
ACTIVE_NOT_RECRUITING
NTT Medical Center Tokyo
Tokyo
ACTIVE_NOT_RECRUITING
Yamagata University Hospital
Yamagata
University of Fukui Hospital
Yoshida
COMPLETED
South Korea (3)
Seoul National University Hospital
Seoul
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Spain (9)
Hosp Univ Vall D Hebron
Barcelona
Hosp Clinic de Barcelona
Barcelona
Hosp. Gral. Univ. Gregorio Maranon
Madrid
Hospital Infantil Universitario Nino Jesus
Madrid
Hosp Univ Fund Jimenez Diaz
Madrid
Clinica Univ. de Navarra
Pamplona
Hosp Clinico Univ de Salamanca
Salamanca
Hosp. Virgen Del Rocio
Seville
Hosp. Clinico Univ. de Valencia
Valencia
Taiwan (3)
China Medical University Hospital
Taichung
National Cheng Kung University Hospital
Tainan
National Taiwan University Hospital
Taipei
United Kingdom (8)
University Hospital of Wales
Cardiff
Leeds Teaching Hospitals NHS Trust
Leeds
The Clatterbridge Cancer Centre
Liverpool
Guys and St Thomas NHS Foundation Trust
London
University College London Hospitals
London
The Christie Nhs Foundation Trust
Manchester
Oxford University Hospitals NHS Trust
Oxfordshire
University Hospitals Plymouth NHS Trust
Plymouth
United States (27)
University of New Mexico
Albuquerque , New Mexico
Massachusetts General Hospital
Boston , Massachusetts
Dana Farber Cancer Institute
Boston , Massachusetts
Roswell Park Comprehensive Cancer Center
Buffalo , New York
University of Chicago
Chicago , Illinois
Baylor University Medical Center
Dallas , Texas
Karmanos Cancer Institute
Detroit , Michigan
City of Hope
Duarte , California
City of Hope Phoenix
Goodyear , Arizona
TERMINATED
Start Midwest
Grand Rapids , Michigan
Houston Methodist Hospital
Houston , Texas
MD Anderson
Houston , Texas
St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation
Indianapolis , Indiana
University of Tennessee Medical Center
Knoxville , Tennessee
Norton Cancer Institute
Louisville , Kentucky
COMPLETED
Medical College of WI at Froedtert
Milwaukee , Wisconsin
NYU Langone Medical Center
New York , New York
University of California Irvine Medical Center
Orange , California
COMPLETED
Fox Chase Cancer Center
Philadelphia , Pennsylvania
Oregon Health And Science University
Portland , Oregon
Maine Health
Providence , Rhode Island
Virginia Commonwealth University
Richmond , Virginia
San Antonio Methodist TX Transplant Physicians Group