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

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

Primary outcomes

• Number of Participants with Adverse Events (AEs) [Up to 3 years 5 months]: 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.
• Number of Participants with AEs by Severity [Up to 3 years 5 months]: 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.
• Number of Participants with Dose-Limiting Toxicity (DLT) [Cycle 1 (28 days)]: 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.

Secondary outcomes

• Plasma Concentration of JNJ-75276617 [Up to 3 years 5 months]: Plasma concentration of JNJ-75276617 will be reported.
• Number of Participants with Depletion of Leukemic Blasts [Up to 3 years 5 months]: Number of participants with depletion of leukemic blasts will be reported.
• Number of Participants with Differentiation of Leukemic Blasts [Up to 3 years 5 months]: Number of participants with differentiation of leukemic blasts will be reported.
• Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes or Genes Associated With Differentiation [Up to 3 years 5 months]: Changes in expression of menin-histone-lysine N-methyltransferase 2A (KMT2A) target genes or genes associated with differentiation will be reported.
• Overall Response Rate (ORR) per Response Criteria in Acute Myeloid Leukemia (AML) [Up to 3 years 5 months]: 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.
• Overall Response Rate (ORR) per the Response Criteria in B-cell Acute Lymphoblastic Leukemia (ALL) [Up to 3 years 5 months]: 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 to Response (TTR) [Up to 3 years 5 months]: 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.
• Duration of Response (DOR) [Up to 3 years 5 months]: 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.
• Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) [Up to 3 years 5 months]: Percentage of participants who receive an allogeneic HSCT after treatment will be reported.

Sex: All, ages: 30 Days to 30 Years

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)

• Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC