A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia

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

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 Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Leukemias
• 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): 400
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@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
• China
  • Chengdu, China, 610041
    • Recruiting
    • West China Hospital Si Chuan University
  • Guangzhou, China, 510515
    • Recruiting
    • Nanfang Hospital of Southern Medical Hospital
• France
  • Besancon, France, 25000
    • Recruiting
    • Hopital Jean Minjoz
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Nantes Cedex 1, France, 44093
    • Recruiting
    • CHU de Nantes hotel Dieu
  • Paris, France, 75010
    • Recruiting
    • Hôpital 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 Benite, France, 69310
    • Recruiting
    • CHU Lyon Sud
  • Strasbourg, France, 67200
    • Recruiting
    • Institut De Cancerologie Strasbourg Europe ICANS
  • Toulouse, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Tours cedex, France, 37044
    • Recruiting
    • CHU Bretonneau
  • Vandoeuvre les Nancy, France, 54511
    • Recruiting
    • CHRU Nancy 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 Yafo, Israel, 6423906
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Japan
  • Fukushima, Japan, 960 1295
    • Recruiting
    • Fukushima Medical University Hospital
  • Nagoya, Japan, 466-8560
    • Recruiting
    • Nagoya University Hospital
  • Sapporo, Japan, 060-8648
    • Recruiting
    • Hokkaido University Hospital
  • Tokyo, Japan, 141-8625
    • Recruiting
    • NTT Medical Center Tokyo
  • Yoshida, Japan, 910-1193
    • Recruiting
    • University of Fukui Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 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, 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
  • Sevilla, 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
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guys and St Thomas NHS Foundation Trust
  • 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
  • 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
  • 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, 02215
      • 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 York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Maine Health
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center
  • Texas
    • 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:

• Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options
• Participants greater than or equal (>=)12 and less than (<) 18 years of age are only eligible for the Phase 1 adolescent cohort
• 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; Estimated or measured glomerular filtration rate greater than or equal to (>=) 50 milliliter per minute (mL/min) per four variable modified diet in renal disease (MDRD) equation
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent 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 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.

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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2: 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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Estimated): February 16, 2026
• Study Completion (Estimated): October 31, 2027

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 (Estimated): January 10, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Acute Disease
• 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