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

NCT04811560 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: CR10899875276617ALE10012023-506581-31-00
• Study Type: interventional
• Target: 420
• Locations: 13 countries
• Sites: 103

Brief 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.

Conditions

Acute Leukemia

Outcome Measures

Primary Outcomes (4)

• Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

  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.

  Up to 4 years and 9 months

• Phase 1: Number of Participants with AEs by Severity

  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.

  Up to 4 years and 9 months

• Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT)

  Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.

  Up to 28 days Cycle 1

• Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh)

  Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment.

  Up to 4 years and 9 months

Secondary Outcomes (11)

• Phase 1 and 2: Plasma Concentration of Bleximenib

  Up to 4 years and 9 months

• Phase 1 and 2: Overall Response Rate (ORR)

  Up to 4 years and 9 months

• Phase 1: Duration of Response (DOR)

  Up to 4 years and 9 months

• Phase 1 and 2: Time To Response (TTR)

  Up to 4 years and 9 months

• Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh)

  Up to 4 years and 9 months

Study Arms (1)

Bleximenib

EXPERIMENTAL

Participants in Phase 1 Part 1 (dose escalation) will receive bleximenib orally. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) have been identified. Participants in Phase 1 Part 2 (dose expansion) will receive bleximenib orally at the RP2D(s) determined in Part 1. In Phase 2 participants will receive bleximenib at the RP2D to evaluate anti-leukemia activity and demonstrate acceptable safety at the RP2D(s).

Drug: Bleximenib

Interventions

Bleximenib DRUG

Bleximenib is administered orally.

Also known as: JNJ-75276617

Bleximenib

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (103)

City of Hope Phoenix

Goodyear, Arizona, 85338, United States

TERMINATED

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of California Irvine Medical Center

Orange, California, 92868, United States

COMPLETED

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, 46237, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

COMPLETED

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201 2013, United States

RECRUITING

Start Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87131, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

NYU Langone Medical Center

New York, New York, 10016, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Oregon Health And Science University

Portland, Oregon, 97239, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Maine Health

Providence, Rhode Island, 02903, United States

RECRUITING

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

RECRUITING

Baylor University Medical Center

Dallas, Texas, 75246, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030-2740, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

San Antonio Methodist TX Transplant Physicians Group

San Antonio, Texas, 78229, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

Medical College of WI at Froedtert

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Monash Medical Centre

Clayton, 3168, Australia

RECRUITING

Royal Perth Hospital

Perth, 6000, Australia

RECRUITING

Gold Coast University Hospital

Southport, 4211, Australia

RECRUITING

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

Instituto D Or de Pesquisa e Ensino

Brasília, 70390 700, Brazil

RECRUITING

Liga Norte Riograndense Contra O Cancer

Natal, 59062 000, Brazil

RECRUITING

Ministerio da Saude Instituto Nacional do Cancer

Rio de Janeiro, 20230 130, Brazil

RECRUITING

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

São Paulo, 01246 000, Brazil

RECRUITING

Instituto D Or de Pesquisa e Ensino IDOR

São Paulo, 01401 002, Brazil

RECRUITING

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900, Brazil

RECRUITING

Vancouver Coastal Health

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

Hopital Maisonneuve Rosemont

Montreal, Quebec, H1T 2M4, Canada

RECRUITING

Peking University First Hospital

Beijing, 100034, China

RECRUITING

The First Hospital of Jilin University

Changchun, 130021, China

RECRUITING

West China Hospital Si Chuan University

Chengdu, 610041, China

RECRUITING

Nanfang Hospital of Southern Medical Hospital

Guangzhou, 510515, China

RECRUITING

First Affiliated Hospital Medical School of Zhejiang University

Hangzhou, 310009, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, 250012, China

RECRUITING

The First Affiliated Hospital of NanChang University

Nanchang, 330006, China

RECRUITING

Zhongda Hospital Southeast University

Nanjing, 210009, China

RECRUITING

Institute of Hematology and Blood Diseases Hospital

Tianjin, 301609, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, 325000, China

RECRUITING

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

Wuhan, 430022, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, 450003, China

RECRUITING

Hopital Jean Minjoz

Besançon, 25000, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

CHU de Nantes hotel Dieu

Nantes, 44093, France

RECRUITING

Hopital Saint Louis

Paris, 75010, France

RECRUITING

Hopital trousseau- APHP

Paris, 75012, France

RECRUITING

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

Pessac, 33604, France

COMPLETED

CHU Lyon Sud

Pierre-Bénite, 69310, France

RECRUITING

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67098, France

RECRUITING

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059, France

RECRUITING

CHU Bretonneau

Tours, 37044, France

RECRUITING

CHRU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Carmel Medical Center

Haifa, 3436212, Israel

RECRUITING

Hadassah University Hospita Ein Kerem

Jerusalem, 9112001, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 52621, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

RECRUITING

Kyushu University Hospital

Fukuoka, 812-0054, Japan

ACTIVE NOT RECRUITING

Fukushima Medical University Hospital

Fukushima, 960 1295, Japan

ACTIVE NOT RECRUITING

Kanazawa University Hospital

Kanazawa, 920 8641, Japan

ACTIVE NOT RECRUITING

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

ACTIVE NOT RECRUITING

Kobe City Medical Center General Hospital

Kobe, 650 0047, Japan

ACTIVE NOT RECRUITING

Gunmaken Saiseikai Maebashi Hospital

Maebashi, 371-0821, Japan

ACTIVE NOT RECRUITING

Nagoya University Hospital

Nagoya, 466-8560, Japan

COMPLETED

Hokkaido University Hospital

Sapporo, 060-8648, Japan

ACTIVE NOT RECRUITING

NTT Medical Center Tokyo

Tokyo, 141-8625, Japan

ACTIVE NOT RECRUITING

Yamagata University Hospital

Yamagata, 990 2331, Japan

RECRUITING

University of Fukui Hospital

Yoshida, 910-1193, Japan

COMPLETED

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

RECRUITING

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

RECRUITING

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

RECRUITING

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Clinica Univ. de Navarra

Pamplona, 31008, Spain

RECRUITING

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

RECRUITING

Hosp. Virgen Del Rocio

Seville, 41013, Spain

RECRUITING

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

RECRUITING

China Medical University Hospital

Taichung, 404327, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10043, Taiwan

RECRUITING

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

RECRUITING

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre

Liverpool, L7 8YA, United Kingdom

RECRUITING

Guys and St Thomas NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

University College London Hospitals

London, W1T 7HA, United Kingdom

RECRUITING

The Christie Nhs Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

Oxford University Hospitals NHS Trust

Oxfordshire, OX3 7LE, United Kingdom

RECRUITING

University Hospitals Plymouth NHS Trust

Plymouth, PL6 8DH, United Kingdom

RECRUITING

Related Publications (1)

• Kwon MC, Thuring JW, Querolle O, Dai X, Verhulst T, Pande V, Marien A, Goffin D, Wenge DV, Yue H, Cutler JA, Jin C, Perner F, Hogeling SM, Shaffer PL, Jacobs F, Vinken P, Cai W, Keersmaekers V, Eyassu F, Bhogal B, Verstraeten K, El Ashkar S, Perry JA, Jayaguru P, Barreyro L, Kuchnio A, Darville N, Krosky D, Urbanietz G, Verbist B, Edwards JP, Cowley GS, Kirkpatrick R, Steele R, Ferrante L, Guttke C, Daskalakis N, Pietsch EC, Wilson DM, Attar R, Elsayed Y, Fischer ES, Schuringa JJ, Armstrong SA, Packman K, Philippar U. Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias. Blood. 2024 Sep 12;144(11):1206-1220. doi: 10.1182/blood.2023022480.

  PMID: 38905635 DERIVED

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 23, 2021
• Study Start: May 19, 2021
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): September 22, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

JP (11); BR (6); ES (9); FR (13); IL (4); KR (3); US (27); AU (3); CA (3); BE (1); GB (8); CN (12); TW (3)