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RecruitingNCT06575296

Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant

A Phase I Study of SNDX 5613 (Revumenib) as Post-Transplant Maintenance After Allogeneic Hematopoietic Cell Transplant in Patients With KMT2A-Rearranged or NPM1-Mutated Acute Leukemia

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
27 (estimated)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
2 Years
Healthy volunteers
Not accepted

Summary

This phase I trial tests the safety, side effects, best dose and effectiveness of revumenib in treating patients with acute leukemia after allogeneic stem cell transplant. Revumenib is in a class of medications called menin inhibitors. Revumenib targets and binds to the protein menin, thereby preventing the interaction between menin and the mixed lineage leukemia protein. Disrupting this interaction prevents the activation of specific genes that fuel the development of leukemia cells and inhibits the survival, growth, and production of certain kinds of leukemia cells. Giving revumenib may be safe, tolerable, and/or effective in treating patients with acute leukemia after allogeneic stem cell transplant.

Detailed description

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of revumenib as maintenance therapy in patients with KMT2A rearranged or NPM1 mutated acute leukemia after undergoing allogeneic hematopoietic cell transplantation (alloHCT). II. Determine the recommended phase 2 dose (RP2D) of revumenib as maintenance therapy in patients with KMT2A rearranged (KMT2Ar) or NPM1 mutated (NPM1m) acute leukemia after undergoing alloHCT. SECONDARY OBJECTIVES: I. Assess overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR), and composite graft versus host disease (GVHD)-free, relapse-free survival (GRFS) at 1 and 2 years from first dose of revumenib. II. Non-relapse mortality (NRM) at 100 days 1 and 2 years after first dose of revumenib. III. Evaluate the rate and grading of acute GVHD at 180 days after alloHCT. IV. Evaluate the incidence and grading of chronic GVHD (cGVHD) at 1 and 2 years after first dose of revumenib. V. Evaluate minimal residual disease (MRD) using quantitative polymerase chain reaction (PCR) (NPM1m) or ClonoSeq (B-acute lymphoblastic leukemia \[B-ALL\]). VI. Evaluate MRD using flow cytometry. VII. Evaluate the feasibility of maintenance therapy. EXPLORATORY OBJECTIVES: I. Evaluate immune cell populations and immune reconstitution after maintenance therapy. II. Evaluate the inflammatory cytokine profile and levels. III. Evaluate detection of residual NPM1m error-corrected sequencing. IV. Develop and evaluate a novel KMT2Ar assay in detecting residual disease. V. Evaluate quality of life. OUTLINE: This is a dose-escalation study of revumenib followed by a dose-expansion study. Starting 50-150 days after alloHCT, patients receive revumenib orally (PO) once daily (QD) or every 12 hours on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow biopsy during screening and may undergo echocardiography (ECHO) during screening and as clinically indicated. Patients also undergo bone marrow aspiration and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years post-treatment start.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow AspirationUndergo bone marrow aspiration
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy
PROCEDUREEchocardiographyUndergo ECHO
OTHERElectronic Health Record ReviewAncillary studies
OTHERQuality-of-Life AssessmentAncillary studies
OTHERQuestionnaire AdministrationAncillary studies
DRUGRevumenibGiven PO

Timeline

Start date
2024-12-06
Primary completion
2028-04-29
Completion
2028-04-29
First posted
2024-08-28
Last updated
2026-03-05

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT06575296. Inclusion in this directory is not an endorsement.