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

Janssen (J&J Innovative Medicine)

Status and phase: Begins enrollment in a year or more; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05521087

75276617ALE1003 (Other Identifier)

CR109192

2022-000380-46 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 80 estimated patients

Sex: All

Ages: 30 days to 30 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

80 participants in 2 patient groups

Arm A: <2 Years Old

Experimental group

Description:

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.

Treatment:

Drug: JNJ-75276617

Drug: Intrathecal Chemotherapy

Drug: Pegaspargase

Drug: Fludarabine

Drug: Vincristine

Drug: Dexamethasone

Drug: Cytarabine

Arm B: >=2 Years Old

Experimental group

Description:

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.

Treatment:

Drug: JNJ-75276617

Drug: Intrathecal Chemotherapy

Drug: Pegaspargase

Drug: Fludarabine

Drug: Vincristine

Drug: Dexamethasone

Drug: Cytarabine