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

Janssen Research & Development, LLC

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

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

JNJ-75276617DRUG

JNJ-75276617 will be administered orally.

FludarabineDRUG

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

CytarabineDRUG

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

Intrathecal ChemotherapyDRUG

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

DexamethasoneDRUG

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

VincristineDRUG

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

PegaspargaseDRUG

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

Eligibility

Sex: ALLMin age: 30 DaysMax age: 30 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Cycle 1 (28 days)

Secondary Outcomes

Plasma Concentration of JNJ-75276617

Plasma concentration of JNJ-75276617 will be reported.

Time frame: Up to 3 years 5 months

Number of Participants with Depletion of Leukemic Blasts

Number of participants with depletion of leukemic blasts will be reported.

Time frame: Up to 3 years 5 months

Number of Participants with Differentiation of Leukemic Blasts

Number of participants with differentiation of leukemic blasts will be reported.

Time frame: Up to 3 years 5 months

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.

Time frame: Up to 3 years 5 months

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.

Time frame: Up to 3 years 5 months

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.

Time frame: Up to 3 years 5 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.

Time frame: Up to 3 years 5 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.

Time frame: Up to 3 years 5 months

Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Percentage of participants who receive an allogeneic HSCT after treatment will be reported.

Time frame: Up to 3 years 5 months

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes