A Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase I/Ib Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias Harboring KMT2A, NPM1, or Nucleoporin Gene Alterations

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05521087
• Other study ID #: CR109192
• Secondary ID: 2022-000380-4675
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: December 26, 2025
• Est. completion date: January 29, 2030

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) (RP2Ds) of JNJ-75276617 in combination with a conventional chemotherapy backbone in pediatric and young adult participants with relapsed/refractory acute leukemia harboring histone-lysine N-methyltransferase 2A1 ([KMT2A1], nucleophosmin 1 gene (NPM1), or nucleoporin alterations in Part 1 (Dose Escalation) and to further evaluate safety at the RP2D(s) of JNJ-75276617 in combination with chemotherapy in pediatric and young adult participants with relapsed/refractory acute leukemia harboring KMT2A1, NPM1, or nucleoporin alterations and safety at the RP2D(s) of JNJ-75276617 as monotherapy in a select low burden of disease cohort in Part 2 (Dose Expansion).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: January 29, 2030
• Est. primary completion date: September 11, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Days to 30 Years

Eligibility

Inclusion Criteria:

• Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A) or nucleophosmin 1 gene (NPM1) or nucleoporin (NUP98 or NUP214) alterations
• Performance status greater than or equal to (>=) 50 by lansky scale (for participants less than [<] 16 years of age) or >=50 percent (%) karnofsky scale (for participants >=16 years of age)
• Estimated or measured glomerular filtration rate >= 60 milliliter per minute per 1.73 meter square (mL/min/1.73m^2) based on the bed side schwartz formula

Exclusion Criteria:

• Received an allogeneic hematopoietic transplant within 60 days of screening
• Active acute graft-versus-host disease of any grade or chronic graft-versus-host which is not well-controlled
• Received immunosuppressive therapy post hematopoietic transplant within 30 days of enrollment
• Diagnosis of Down syndrome associated leukemia, acute promyelocytic leukemia, juvenile myelomonocytic leukemia
• Diagnosis of fanconi anemia, kostmann syndrome, shwachman diamond syndrome, or any other known bone marrow failure syndrome
• Prior exposure to menin-KMT2A inhibitors
• Prior cancer immunotherapy (ie [that is], Chimeric Antigen Receptor-T Cell Therapy [CAR-T], inotuzumab, gemtuzumab ozogamicin) 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 Leukemia of Ambiguous Lineage
• Acute Leukemias
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• JNJ-75276617
JNJ-75276617 will be administered orally.
• Fludarabine
Fludarabine chemotherapy will be administered as intravenous (IV) infusion for participants with AML.
• Cytarabine
Cytarabine chemotherapy will be administered as IV infusion for participants with AML.
• Intrathecal Chemotherapy
Intrathecal chemotherapy will be administered as IV infusion for participants with AML or B-cell ALL.
• Dexamethasone
Dexamethasone chemotherapy will be administered as IV infusion for participants with B-cell ALL.
• Vincristine
Vincristine chemotherapy will be administered as IV infusion for participants with B-cell ALL.
• Pegaspargase
Pegaspargase chemotherapy will be administered as IV infusion for participants with B-cell ALL.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	UNC Hospitals - N.C. Childrens Hospital	Chapel Hill	North Carolina
United States	Atrium Health	Charlotte	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	St Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Wisconsin - Milwaukee Hospital	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering	New York	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs)	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 3 years 5 months
Primary	Number of Participants with AEs by Severity	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. 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 3 years 5 months
Primary	Number of Participants with Dose-Limiting Toxicity (DLT)	Percentage of participants with DLT will be assessed. The DLTs are specific adverse events related to JNJ-75276617 and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.	Cycle 1 (28 days)
Secondary	Plasma Concentration of JNJ-75276617	Plasma concentration of JNJ-75276617 will be reported.	Up to 3 years 5 months
Secondary	Number of Participants with Depletion of Leukemic Blasts	Number of participants with depletion of leukemic blasts will be reported.	Up to 3 years 5 months
Secondary	Number of Participants with Differentiation of Leukemic Blasts	Number of participants with differentiation of leukemic blasts will be reported.	Up to 3 years 5 months
Secondary	Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation	Changes in expression of menin-histone-lysine N-methyltransferase 2A (KMT2A) target genes or genes associated with differentiation will be reported.	Up to 3 years 5 months
Secondary	Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML)	ORR is defined as the percentage of participants who achieve complete response (CR), CR with incomplete hematologic recovery (CRi) or CR with partial hematologic recovery (CRh) per the Response Criteria in AML.	Up to 3 years 5 months
Secondary	Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL)	ORR in participants with B-cell ALL is defined as the percentage of participants who achieve CR or CRi per the response criteria in B-cell ALL.	Up to 3 years 5 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 3 years 5 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 3 years 5 months
Secondary	Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)	Percentage of participants who receive an allogeneic HSCT after treatment will be reported.	Up to 3 years 5 months