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NCT04811560PHASE1, PHASE2Recruiting

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

Janssen Research & Development, LLC

Start Date

5/19/2021

Completion Date

9/22/2030

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 Criteria

Age Range: 2 years to No maximum

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

DRUG

Bleximenib

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Conditions

Acute Leukemia

Locations

City of Hope

Duarte, California 91010

United States

University of California Irvine Medical Center

Orange, California 92868

United States

University of California San Francisco

San Francisco, California 94143

United States

UCSF Benioff Children's Hospital

San Francisco, California 94158

United States

University of Chicago

Chicago, Illinois 60637

United States

St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation

Indianapolis, Indiana 46237

United States

Norton Cancer Institute

Louisville, Kentucky 40207

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02115

United States

Karmanos Cancer Institute

Detroit, Michigan 48201 2013

United States

Start Midwest

Grand Rapids, Michigan 49546

United States

University of New Mexico

Albuquerque, New Mexico 87131

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York 14263

United States

NYU Langone Medical Center

New York, New York 10016

United States

Montefiore Medical Center

The Bronx, New York 10467

United States

Oregon Health And Science University

Portland, Oregon 97239

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania 19111

United States

Maine Health

Providence, Rhode Island 02903

United States

University of Tennessee Medical Center

Knoxville, Tennessee 37920

United States

Baylor University Medical Center

Dallas, Texas 75246

United States

Houston Methodist Hospital

Houston, Texas 77030-2740

United States

MD Anderson

Houston, Texas 77030

United States

San Antonio Methodist TX Transplant Physicians Group

San Antonio, Texas 78229

United States

Virginia Commonwealth University

Richmond, Virginia 23298

United States

Swedish Cancer Institute

Seattle, Washington 98104

United States

Medical College of WI at Froedtert

Milwaukee, Wisconsin 53226

United States

Monash Medical Centre

Clayton, 3168

Australia

Royal Perth Hospital

Perth, 6000

Australia

Gold Coast University Hospital

Southport, 4211

Australia

Ghent University Hospital

Ghent, 9000

Belgium

Instituto D Or de Pesquisa e Ensino

Brasília, 70390 700

Brazil

Liga Norte Riograndense Contra O Cancer

Natal, 59062 000

Brazil

Ministerio da Saude Instituto Nacional do Cancer

Rio de Janeiro, 20230 130

Brazil

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

São Paulo, 01246 000

Brazil

Instituto D Or de Pesquisa e Ensino IDOR

São Paulo, 01401 002

Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900

Brazil

Vancouver Coastal Health

Vancouver, British Columbia V5Z 1M9

Canada

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario M5G 1X6

Canada

Hopital Maisonneuve Rosemont

Montreal, Quebec H1T 2M4

Canada

Peking University First Hospital

Beijing, 100034

China

The First Hospital of Jilin University

Changchun, 130021

China

West China Hospital Si Chuan University

Chengdu, 610041

China

Nanfang Hospital of Southern Medical Hospital

Guangzhou, 510515

China

First Affiliated Hospital Medical School of Zhejiang University

Hangzhou, 310009

China

Qilu Hospital of Shandong University

Jinan, 250012

China

The First Affiliated Hospital of NanChang University

Nanchang, 330006

China

Zhongda Hospital Southeast University

Nanjing, 210009

China

Institute of Hematology and Blood Diseases Hospital

Tianjin, 301609

China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325000

China

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

Wuhan, 430022

China

Henan Cancer Hospital

Zhengzhou, 450003

China

Hopital Jean Minjoz

Besançon, 25000

France

Institut Paoli Calmettes

Marseille, 13009

France

CHU de Nantes hotel Dieu

Nantes, 44093

France

Hopital Saint Louis

Paris, 75010

France

Hopital trousseau- APHP

Paris, 75012

France

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

Pessac, 33604

France

CHU Lyon Sud

Pierre-Bénite, 69310

France

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67098

France

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059

France

CHU Bretonneau

Tours, 37044

France

CHRU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54500

France

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, 54511

France

Gustave Roussy

Villejuif, 94805

France

Carmel Medical Center

Haifa, 3436212

Israel

Hadassah University Hospita Ein Kerem

Jerusalem, 9112001

Israel

Sheba Medical Center

Ramat Gan, 52621

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906

Israel

Kyushu University Hospital

Fukuoka, 812-0054

Japan

Fukushima Medical University Hospital

Fukushima, 960 1295

Japan

Kanazawa University Hospital

Kanazawa, 920 8641

Japan

National Cancer Center Hospital East

Kashiwa, 277-8577

Japan

Kobe City Medical Center General Hospital

Kobe, 650 0047

Japan

Gunmaken Saiseikai Maebashi Hospital

Maebashi, 371-0821

Japan

Nagoya University Hospital

Nagoya, 466-8560

Japan

Hokkaido University Hospital

Sapporo, 060-8648

Japan

NTT Medical Center Tokyo

Tokyo, 141-8625

Japan

Yamagata University Hospital

Yamagata, 990 2331

Japan

University of Fukui Hospital

Yoshida, 910-1193

Japan

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hosp Univ Vall D Hebron

Barcelona, 08035

Spain

Hosp Clinic de Barcelona

Barcelona, 08036

Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007

Spain

Hospital Infantil Universitario Nino Jesus

Madrid, 28009

Spain

Hosp Univ Fund Jimenez Diaz

Madrid, 28040

Spain

Clinica Univ. de Navarra

Pamplona, 31008

Spain

Hosp Clinico Univ de Salamanca

Salamanca, 37007

Spain

Hosp. Virgen Del Rocio

Seville, 41013

Spain

Hosp. Clinico Univ. de Valencia

Valencia, 46010

Spain

China Medical University Hospital

Taichung, 404327

Taiwan

National Cheng Kung University Hospital

Tainan, 704

Taiwan

National Taiwan University Hospital

Taipei, 10043

Taiwan

University Hospital of Wales

Cardiff, CF14 4XW

United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF

United Kingdom

The Clatterbridge Cancer Centre

Liverpool, L7 8YA

United Kingdom

Guys and St Thomas NHS Foundation Trust

London, SE1 9RT

United Kingdom

University College London Hospitals

London, W1T 7HA

United Kingdom

The Christie Nhs Foundation Trust

Manchester, M20 4BX

United Kingdom

Oxford University Hospitals NHS Trust

Oxfordshire, OX3 7LE

United Kingdom

University Hospitals Plymouth NHS Trust

Plymouth, PL6 8DH

United Kingdom