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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia
• Intervention / Treatment: Drug: Bleximenib

Detailed Description

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by uncontrolled clonal expansion of hematopoietic progenitor cells (myeloid blasts) in the peripheral blood, bone marrow, and other tissues. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy propagated by impaired differentiation, proliferation, and accumulation of lymphoid progenitor cells in the bone marrow and/or extramedullary sites. JNJ-75276617 is an orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between histone-lysine N-methyltransferase 2A ([KMT2A], also called mixed-lineage leukemia 1 [MLL1]; wild-type and fusion) and menin, with activity in leukemic cell lines and primary leukemia patient or patient-derived samples with either KMT2A alterations including gene rearrangements (KMT2A-r), duplications, and amplification, or nucleophosmin 1 gene (NPM1) alterations. The primary goal of this FIH study is to establish the recommended Phase 2 dose (RP2D) of JNJ-75276617 with an acceptable safety profile. The total duration of the study is up to 4 years and 9 months. Safety assessment will include adverse events (AEs), serious adverse events (SAEs), physical examination, Eastern Cooperative Oncology Group (ECOG) performance status, vital signs, electrocardiogram, clinical safety laboratory assessment and pregnancy testing.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Medical Centre
  • Perth, Australia, 6000
    • Recruiting
    • Royal Perth Hospital
  • Southport, Australia, 4211
    • Recruiting
    • Gold Coast University Hospital
• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Ghent University Hospital
• Brazil
  • Brasília, Brazil, 70390 700
    • Recruiting
    • Instituto D Or de Pesquisa e Ensino
  • Natal, Brazil, 59062 000
    • Recruiting
    • Liga Norte Riograndense Contra o Câncer
  • Rio de Janeiro, Brazil, 20230 130
    • Recruiting
    • Ministerio da Saude Instituto Nacional do Cancer
  • São Paulo, Brazil, 01509 900
    • Recruiting
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • São Paulo, Brazil, 01246 000
    • Recruiting
    • Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo
  • São Paulo, Brazil, 01401 002
    • Recruiting
    • Instituto D Or de Pesquisa e Ensino IDOR
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver Coastal Health
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X6
      • Recruiting
      • Princess Margaret Cancer Centre University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • Hopital Maisonneuve Rosemont
• China
  • Beijing, China, 100034
    • Recruiting
    • Peking University First Hospital
  • Changchun, China, 130021
    • Recruiting
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • Recruiting
    • West China Hospital Si Chuan University
  • Guangzhou, China, 510515
    • Recruiting
    • Nanfang Hospital of Southern Medical Hospital
  • Hangzhou, China, 310009
    • Recruiting
    • First Affiliated Hospital Medical School of Zhejiang University
  • Jinan, China, 250012
    • Recruiting
    • Qilu Hospital of Shandong University
  • Nanchang, China, 330006
    • Recruiting
    • The First Affiliated Hospital of Nanchang University
  • Nanjing, China, 210009
    • Recruiting
    • Zhongda Hospital Southeast University
  • Tianjin, China, 301609
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital
  • Wenzhou, China, 325000
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430022
    • Recruiting
    • Union Hospital Tongji Medical College of Huazhong University of Science and Technology
  • Zhengzhou, China, 450003
    • Recruiting
    • Henan Cancer Hospital
• France
  • Besançon, France, 25000
    • Recruiting
    • Hôpital Jean Minjoz
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Nantes, France, 44093
    • Recruiting
    • CHU de Nantes hotel Dieu
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
  • Paris, France, 75012
    • Recruiting
    • Hopital trousseau- APHP
  • Pessac, France, 33604
    • Completed
    • Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
  • Pierre-Bénite, France, 69310
    • Recruiting
    • CHU Lyon Sud
  • Strasbourg, France, 67098
    • Recruiting
    • Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
  • Toulouse, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Tours, France, 37044
    • Recruiting
    • CHU Bretonneau
  • Vandœuvre-lès-Nancy, France, 54511
    • Recruiting
    • CHRU Nancy Brabois
  • Vandœuvre-lès-Nancy, France, 54500
    • Recruiting
    • CHRU de Nancy - Hôpitaux de Brabois
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Israel
  • Haifa, Israel, 3436212
    • Recruiting
    • Carmel Medical Center
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah University Hospita Ein Kerem
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Japan
  • Fukuoka, Japan, 812-0054
    • Active, not recruiting
    • Kyushu University Hospital
  • Fukushima, Japan, 960 1295
    • Active, not recruiting
    • Fukushima Medical University Hospital
  • Kanazawa, Japan, 920 8641
    • Active, not recruiting
    • Kanazawa University Hospital
  • Kashiwa, Japan, 277-8577
    • Active, not recruiting
    • National Cancer Center Hospital East
  • Kobe, Japan, 650 0047
    • Active, not recruiting
    • Kobe City Medical Center General Hospital
  • Maebashi, Japan, 371-0821
    • Active, not recruiting
    • Gunmaken Saiseikai Maebashi Hospital
  • Nagoya, Japan, 466-8560
    • Completed
    • Nagoya University Hospital
  • Sapporo, Japan, 060-8648
    • Active, not recruiting
    • Hokkaido University Hospital
  • Tokyo, Japan, 141-8625
    • Active, not recruiting
    • Ntt Medical Center Tokyo
  • Yamagata, Japan, 990 2331
    • Completed
    • Yamagata University Hospital
  • Yoshida, Japan, 910-1193
    • Completed
    • University of Fukui Hospital
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Recruiting
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital Infantil Universitario Nino Jesus
  • Madrid, Spain, 28007
    • Recruiting
    • Hosp. Gral. Univ. Gregorio Maranon
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp Clinico Univ de Salamanca
  • Seville, Spain, 41013
    • Recruiting
    • Hosp. Virgen Del Rocio
  • Valencia, Spain, 46010
    • Recruiting
    • Hosp. Clinico Univ. de Valencia
• Taiwan
  • Taichung, Taiwan, 404327
    • Recruiting
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10043
    • Recruiting
    • National Taiwan University Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • University Hospital of Wales
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • Leeds Teaching Hospitals NHS Trust
  • Liverpool, United Kingdom, L7 8YA
    • Recruiting
    • The Clatterbridge Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guys and St Thomas NHS Foundation Trust
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
  • Oxfordshire, United Kingdom, OX3 7LE
    • Recruiting
    • Oxford University Hospitals NHS Trust
  • Plymouth, United Kingdom, PL6 8DH
    • Recruiting
    • University Hospitals Plymouth NHS Trust
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Terminated
      • City of Hope Phoenix
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
    • Orange, California, United States, 92868
      • Completed
      • University of California Irvine Medical Center
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Benioff Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Recruiting
      • St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Completed
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201 2013
      • Recruiting
      • Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Recruiting
      • University of New Mexico
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Maine Health
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson
    • Houston, Texas, United States, 77030-2740
      • Recruiting
      • Houston Methodist Hospital
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • San Antonio Methodist TX Transplant Physicians Group
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of WI at Froedtert

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bleximenib; 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; Bleximenib is administered orally.; Other Names: JNJ-75276617

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2: Time To Response (TTR)	TTR is defined for the responders as the time from the date of the first dose of bleximenib to the date of the first documented response.	Up to 4 years and 9 months
Phase 2: Event-free survival (EFS)	EFS is defined as the time from the date of first dose of study treatment to the date of treatment failure, relapse, or death due to any cause, whichever occurs first.	Up to 4 years and 9 months
Phase 2: Overall survival (OS)	OS is defined from the date of first dose of study treatment to the date of death due to any cause.	Up to 4 years and 9 months
Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi	MRD-negative rate is defined as the percentage of participants who are MRD-negative at any timepoint after the first dose of bleximenib in the responders.	Up to 4 years and 9 months
Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A Serious AE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Up to 4 years and 9 months
Phase 2: Number of Participants Reporting Transfusion Independence	Transfusion independence is defined as independence from red blood cells (RBC) and platelet transfusions during any 56-day interval after receiving study treatment.	Up to 4 years and 9 months
Phase 1 and 2: Plasma Concentration of Bleximenib	Plasma concentration of bleximenib will be reported.	Up to 4 years and 9 months
Phase 1 and 2: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve any response.	Up to 4 years and 9 months
Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh)	The duration of CR/CRh is defined from the date of first CR or CRh response achieved to the date of first evidence of relapsed disease or death due to any cause, whichever occurs first, for participants who achieve a CR or CRh.	Up to 4 years and 9 months
Phase 2: Time To CR/CRh	Time to CR/CRh is defined for responders as the time from the date of the first dose of bleximenib to the date of first achieving either CR or CRh, depending on which milestone is reached.	Up to 4 years and 9 months
Phase 1: Duration of Response (DOR)	DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first.	Up to 4 years and 9 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): September 22, 2030

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: CR108998; 75276617ALE1001 (Other Identifier: Janssen Research & Development, LLC); 2023-506581-31-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No