NCT07498465

A Study to Find the Highest Dose of SNDX-5613 (Revumenib) as a Treatment Option After Hematopoietic Stem Cell Transplant in Children With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia

A Phase 1 Trial of the Menin Inhibitor SNDX-5613 (Revumenib) (NSC# 852942) for Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients With Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Mixed Phenotype Acute Leukemia

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 30 Days – 22 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, best dose, and effectiveness of revumenib given as maintenance therapy after standard hematopoietic stem cell transplant (HSCT) in patients with acute lymphoblastic leukemia, acute myeloid leukemia, or mixed phenotype acute leukemia. Revumenib binds to a protein called menin, which prevents menin from interacting with another protein called MLL. This results in an inhibition of the proliferation of leukemic cells with certain genetic alterations. Revumenib may inhibit the survival, growth, transformation and proliferation of certain kinds of leukemia cells. It is approved for the treatment of patients with certain types of acute leukemia, but it is not approved for maintenance therapy (treatment that aims to prevent cancer from coming back) after HSCT.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of revumenib monotherapy administered as maintenance therapy, orally post-HSCT, on continuous 28-day cycles for patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or mixed phenotype acute leukemia (MPAL). II. To characterize the steady state pharmacokinetics of revumenib administered as post-HSCT maintenance in children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or mixed phenotype acute leukemia (MPAL). SECONDARY OBJECTIVES: I. To preliminarily estimate the 2-year relapse free survival of patients receiving revumenib as post-HSCT maintenance therapy at the MTD/RP2D, within the confines of a phase 1 study. II. To describe treatment related adverse events in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy up to 12 cycles. III. To estimate the proportion of patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy who complete 12 cycles of maintenance therapy. IV. To estimate the proportion of patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy who discontinue therapy due to treatment related adverse events. EXPLORATORY OBJECTIVES: I. To estimate the cumulative incidence of transplant-related mortality in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles. II. To estimate the cumulative incidence of transplant-related relapse in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles. III. To preliminarily estimate overall survival and disease-free survival in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles, within the confines of a phase 1 study. IV. To estimate the cumulative incidence of acute and chronic graft versus host disease (GVHD) in patients with ALL, AML, or MPAL receiving revumenib post-HSCT as maintenance therapy for up to 12-cycles. OUTLINE: This is a dose-escalation study of revumenib followed by a dose-expansion study. Starting 42-100 days after HSCT, patients receive revumenib orally (PO) or via nasogastric (NG)- or gastric (G)-tube every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive optional intrathecal therapy (methotrexate intrathecally \[IT\] or cytarabine IT or methotrexate, hydrocortisone, and cytarabine IT) at the discretion of the physician on study. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial. Patients may undergo echocardiography (ECHO) and radiologic assessment as clinically indicated. After completion of study treatment, patients are followed for up to 1 year.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Childhood Acute Lymphoblastic Leukemia
• Childhood Acute Myeloid Leukemia
• Childhood Mixed Phenotype Acute Leukemia
• Mixed Phenotype Acute Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Cytarabine	Given IT
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Methotrexate	Given IT
PROCEDURE	Radiologic Examination	Undergo radiologic assessment
DRUG	Revumenib	Given PO or via NG- or G-tube
DRUG	Therapeutic Hydrocortisone	Given IT

Timeline

• Start date: 2026-09-10
• Primary completion: 2028-11-12
• Completion: 2028-11-12
• First posted: 2026-03-27
• Last updated: 2026-03-27

Regulatory

• FDA-regulated drug study