RecruitingPhase 1Phase 2NCT04811560

A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)

A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia (cAMeLot-1)


Sponsor

Janssen Research & Development, LLC

Enrollment

400 participants

Start Date

May 19, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

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

Min Age: 2 Years

Inclusion Criteria13

  • Phase 1:
  • Age 2 years and above (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 less than or equal to (\<=) 20\*10\^9/liter (L) and (b) renal function; For adult participants, estimated or measured glomerular filtration rate greater than equal (\>=) 30 milliliter per minute (mL/min) per four variable MDRD equation. For pediatric participants an estimated or measured glomerular filtration rate \>50 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 less than \[\<\]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 Criteria5

  • 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
  • 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

DRUGBleximenib

Bleximenib is administered orally.


Locations(101)

City of Hope Phoenix

Goodyear, Arizona, United States

City of Hope

Duarte, California, United States

University of California Irvine Medical Center

Orange, California, United States

University of California San Francisco

San Francisco, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

University of Chicago

Chicago, Illinois, United States

St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Start Midwest

Grand Rapids, Michigan, United States

University of New Mexico

Albuquerque, New Mexico, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

NYU Langone Medical Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Oregon Health And Science University

Portland, Oregon, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Maine Health

Providence, Rhode Island, United States

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Baylor University Medical Center

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

MD Anderson

Houston, Texas, United States

San Antonio Methodist TX Transplant Physicians Group

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Swedish Cancer Institute

Seattle, Washington, United States

Medical College of WI at Froedtert

Milwaukee, Wisconsin, United States

Monash Medical Centre

Clayton, Australia

Royal Perth Hospital

Perth, Australia

Gold Coast University Hospital

Southport, Australia

Instituto D Or de Pesquisa e Ensino

Brasília, Brazil

Liga Norte Riograndense Contra O Cancer

Natal, Brazil

Ministerio da Saude Instituto Nacional do Cancer

Rio de Janeiro, Brazil

Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo

São Paulo, Brazil

Instituto D Or de Pesquisa e Ensino IDOR

São Paulo, Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, Brazil

Vancouver Coastal Health

Vancouver, British Columbia, Canada

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, Canada

Hopital Maisonneuve Rosemont

Montreal, Quebec, Canada

Peking University First Hospital

Beijing, China

The First Hospital of Jilin University

Changchun, China

West China Hospital Si Chuan University

Chengdu, China

Nanfang Hospital of Southern Medical Hospital

Guangzhou, China

First Affiliated Hospital Medical School of Zhejiang University

Hangzhou, China

Qilu Hospital of Shandong University

Jinan, China

The First Affiliated Hospital of NanChang University

Nanchang, China

Zhongda Hospital Southeast University

Nanjing, China

Institute of Hematology and Blood Diseases Hospital

Tianjin, China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, China

Union Hospital Tongji Medical College of Huazhong University of Science and Technology

Wuhan, China

Henan Cancer Hospital

Zhengzhou, China

Hopital Jean Minjoz

Besançon, France

Institut Paoli Calmettes

Marseille, France

CHU de Nantes hotel Dieu

Nantes, France

Hopital Saint Louis

Paris, France

Hopital trousseau- APHP

Paris, France

Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie

Pessac, France

CHU Lyon Sud

Pierre-Bénite, France

Institut de Cancerologie Strasbourg Europe ICANS

Strasbourg, France

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, France

CHU Bretonneau

Tours, France

CHRU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, France

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, France

Gustave Roussy

Villejuif, France

Carmel Medical Center

Haifa, Israel

Hadassah University Hospita Ein Kerem

Jerusalem, Israel

Sheba Medical Center

Ramat Gan, Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Kyushu University Hospital

Fukuoka, Japan

Fukushima Medical University Hospital

Fukushima, Japan

Kanazawa University Hospital

Kanazawa, Japan

National Cancer Center Hospital East

Kashiwa, Japan

Kobe City Medical Center General Hospital

Kobe, Japan

Gunmaken Saiseikai Maebashi Hospital

Maebashi, Japan

Nagoya University Hospital

Nagoya, Japan

Hokkaido University Hospital

Sapporo, Japan

NTT Medical Center Tokyo

Tokyo, Japan

Yamagata University Hospital

Yamagata, Japan

University of Fukui Hospital

Yoshida, Japan

Seoul National University Hospital

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Hosp Univ Vall D Hebron

Barcelona, Spain

Hosp Clinic de Barcelona

Barcelona, Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, Spain

Hosp Univ Fund Jimenez Diaz

Madrid, Spain

Clinica Univ. de Navarra

Pamplona, Spain

Hosp Clinico Univ de Salamanca

Salamanca, Spain

Hosp. Virgen Del Rocio

Seville, Spain

Hosp. Clinico Univ. de Valencia

Valencia, Spain

China Medical University Hospital

Taichung, Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

University Hospital of Wales

Cardiff, United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

The Clatterbridge Cancer Centre

Liverpool, United Kingdom

Guys and St Thomas NHS Foundation Trust

London, United Kingdom

University College London Hospitals

London, United Kingdom

The Christie Nhs Foundation Trust

Manchester, United Kingdom

Oxford University Hospitals NHS Trust

Oxfordshire, United Kingdom

University Hospitals Plymouth NHS Trust

Plymouth, United Kingdom

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NCT04811560


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