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

NCT05521087 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: CR10919275276617ALE10032022-000380-46
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Acute Leukemias; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Leukemia of Ambiguous Lineage

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (9)

• Plasma Concentration of JNJ-75276617

  Up to 3 years 5 months

• Number of Participants with Depletion of Leukemic Blasts

  Up to 3 years 5 months

• Number of Participants with Differentiation of Leukemic Blasts

  Up to 3 years 5 months

• Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation

  Up to 3 years 5 months

• Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML)

  Up to 3 years 5 months

Study Arms (2)

Arm A: <2 Years Old

EXPERIMENTAL

Participants aged less than (\<) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further 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 dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion of the study, in 3 cohorts divided on the basis of disease diagnosis. Participants with acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL) will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617.

Drug: JNJ-75276617; Drug: Fludarabine; Drug: Cytarabine; Drug: Intrathecal Chemotherapy; Drug: Dexamethasone; Drug: Vincristine; Drug: Pegaspargase

Arm B: >=2 Years Old

EXPERIMENTAL

Participants aged greater than or equal to (\>=) 2 years old in dose escalation portion of the study will receive JNJ-75276617 orally on a 28-day cycle. Starting dose of JNJ-75276617 is based on the adult dose from the ongoing study NCT04811560 with additional dose reductions based on age. Further dose levels will be escalated based on the DLT evaluation by SET until the RP2Ds has been identified. Participants in dose expansion portion of the study will receive JNJ-75276617 orally at one of the RP2D(s) determined in dose escalation portion, in 3 cohorts divided on the basis of disease diagnosis. Participants with AML and B-cell ALL will receive conventional chemotherapy backbone regimen (dexamethasone, vincristine, pegaspargase, fludarabine, cytarabine and intrathecal chemotherapy) in combination with JNJ-75276617.

Drug: JNJ-75276617; Drug: Fludarabine; Drug: Cytarabine; Drug: Intrathecal Chemotherapy; Drug: Dexamethasone; Drug: Vincristine; Drug: Pegaspargase

Interventions

JNJ-75276617 DRUG

JNJ-75276617 will be administered orally.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Fludarabine DRUG

Fludarabine chemotherapy will be administered as intravenous (IV) infusion for participants with AML.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Cytarabine DRUG

Cytarabine chemotherapy will be administered as IV infusion for participants with AML.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Intrathecal Chemotherapy DRUG

Intrathecal chemotherapy will be administered as IV infusion for participants with AML or B-cell ALL.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Dexamethasone DRUG

Dexamethasone chemotherapy will be administered as IV infusion for participants with B-cell ALL.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Vincristine DRUG

Vincristine chemotherapy will be administered as IV infusion for participants with B-cell ALL.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Pegaspargase DRUG

Pegaspargase chemotherapy will be administered as IV infusion for participants with B-cell ALL.

Arm A: <2 Years Old; Arm B: >=2 Years Old

Eligibility Criteria

• Age: 30 Days - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute

Interventions

fludarabine; Cytarabine; Dexamethasone; Vincristine; pegaspargase

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: August 30, 2022
• Study Start: December 26, 2025
• Primary Completion (Estimated): September 11, 2026
• Study Completion (Estimated): January 29, 2030
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share