A Study of JNJ-75276617 in Participants With Acute Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04811560
• Other study ID #: CR108998
• Secondary ID: 2020-005967-3075
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 19, 2021
• Est. completion date: February 16, 2026

Study information

• Verified date: May 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: February 16, 2026
• Est. primary completion date: February 16, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemias
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton
Australia	Royal Perth Hospital	Perth
Australia	Gold Coast University Hospital	Southport
France	Institut Paoli Calmettes	Marseille
France	CHU de Nantes hotel Dieu	Nantes Cedex 1
France	Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie	Pessac
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse
France	CHU Bretonneau	Tours cedex
Spain	Hosp. Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. Fund. Jimenez Diaz	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	The Christie Nhs Foundation Trust	Manchester
United Kingdom	Oxford University Hospitals NHS Trust	Oxfordshire
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	City of Hope	Duarte	California
United States	MD Anderson	Houston	Texas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Medical College of WI at Froedtert	Milwaukee	Wisconsin
United States	NYU Langone Medical Center	New York	New York
United States	University of California Irvine Medical Center	Orange	California
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Secondary	Plasma Concentration of JNJ-75276617	Plasma concentration of JNJ-75276617 will be reported.	Up to 4 years and 9 months
Secondary	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
Secondary	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
Secondary	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