A Study of JNJ-75276617 in Participants With Acute Leukemia

A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants With Acute Leukemia

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of JNJ-75276617 in Part 1 (Dose Escalation) and to determine safety and tolerability at the RP2D(s) in Part 2 (Dose Expansion).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Leukemias
• Intervention / Treatment: Drug: JNJ-75276617

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): 150
• 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
• France
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Nantes Cedex 1, France, 44093
    • Recruiting
    • CHU de NANTES Hotel Dieu
  • Pessac, France, 33604
    • Recruiting
    • Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
  • Toulouse, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Tours cedex, France, 37044
    • Recruiting
    • CHU Bretonneau
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp. Univ. Fund. Jimenez Diaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's 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
• 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
  • 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
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson
  • 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:

• Relapsed or refractory 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
• 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) (hydroxyurea may be used to lower WBC count at screening and during study; cytoreductive therapy may be considered with sponsor approval; (b) Chemistry: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 * upper limit of normal (ULN), total serum bilirubin <= 1.5 * ULN (participants with elevated bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated bilirubin is within clinically acceptable range) and renal function; Estimated or measured glomerular filtration rate greater than or equal to (>=) 50 milliliter per minute (mL/min)/1.73 meter square (m^2) per four variable modified diet in renal disease (MDRD) equation
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1. 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 participant 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
• A participant must agree to all the following during the study and for 90 days after the last dose of study treatment: (a) wear a condom when engaging in any activity that allows for passage of ejaculate to another person; (b) not to donate sperm or freeze for future use for the purpose of reproduction. In addition, the participant should be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak

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. Willing and able to undergo allogeneic stem cell transplant (if clinically indicated); b. Received prior treatment with allogenic bone marrow or stem cell transplant <=3 months before the first dose of study treatment; c. Has evidence of graft versus host disease; d. Received donor lymphocyte infusion <=1 month before the first dose of study treatment; e. 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: JNJ-75276617; Participants in Part 1 (dose escalation) will receive JNJ-75276617 orally on a 28-day cycle. 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) has been identified. Participants in Part 2 (dose expansion) will receive JNJ-75276617 orally at one of the RP2D(s) determined in Part 1. Food effect cohort (optional) participants will receive JNJ-75276617 orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition.

Drug: JNJ-75276617; JNJ-75276617 is administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT)	Percentage of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.	Up to 28 days Cycle 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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of JNJ-75276617	Plasma concentration of JNJ-75276617 will be reported.	Up to 4 years and 9 months
Overall Response Rate (ORR)	ORR is based on investigator-determined responses and is defined as the percentage of participants who achieve any response.	Up to 4 years and 9 months
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
Time to Response (TTR)	TTR is defined for the responders as the time from the date of the first dose of JNJ-75276617 to the date of the first documented response.	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): February 16, 2026

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): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Acute Disease
• Other Study ID Numbers: CR108998; 2020-005967-30 (EudraCT Number); 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 the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/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