Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant
NCT Number: NCT06575296
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Acute Leukemia|Acute Leukemia of Ambiguous Lineage|Acute Lymphoblastic Leukemia|Acute Myeloid Leukemia|Childhood Acute Leukemia|Childhood Acute Leukemia of Ambiguous Lineage|Childhood Acute Lymphoblastic Leukemia|Childhood Acute Myeloid Leukemia
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|PROCEDURE: Echocardiography|OTHER: Electronic Health Record Review|OTHER: Quality-of-Life Assessment|OTHER: Questionnaire Administration|DRUG: Revumenib
Sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 27
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-25
Completion Date: 2025-12-20
Locations: City of Hope Medical Center, Duarte, California, 91010, United States

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.

Primary Outcome Measures: Incidence of adverse events, Will evaluate toxicity as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5, including dose limiting toxicity (DLT). The toxicity/adverse event information recorded on each subject will include type, severity, duration, and attribution/association with the study regimen and DLT occurrence. Tables will be constructed to summarize the observed incidence, severity, and type of toxicity, including, but not limited to infections, other adverse events of special interest, and serious adverse events., Start of protocol therapy up to 2 years
Secondary Outcome Measures: Molecular response, Will evaluate molecular response using quantitative polymerase chain reaction for NPM1 mutated acute myeloid leukemia and ClonoSeq for B-acute lymphoblastic leukemia, per standard of care., Up to 2 years|Overall survival (OS), OS will be censored at last follow-up if patients are known to be alive. Survival endpoints will be analyzed using Kaplan-Meier curves., Start of protocol therapy to death, assessed up to 2 years|Relapse free survival (RFS), RFS will be censored at last follow-up if patients are alive and relapse/progression-free. Survival endpoints will be analyzed using Kaplan-Meier curves., Start of protocol therapy to relapse/progression or death, assessed up to 2 years|Graft versus host disease (GVHD)-free/relapse survival (GRFS), GRFS will be censored at last follow-up if patients are known to be alive and free of any event of interest. Survival endpoints will be analyzed using Kaplan-Meier curves., Start of protocol therapy to first observation of developing grade 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse/progression, or death, assessed up to 2 years|Cumulative incidence of relapse/progression, Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse/progression are censored at the time of last follow-up. Competing risks endpoints will be analyzed using the curves of cumulative incidence., Start of protocol therapy to relapse/progression, assessed up to 2 years|Cumulative incidence of non-relapse mortality (NRM), Relapse/progression is considered a competing risk. Surviving patients with no history of relapse/progression are censored at the time of last follow-up. Competing risks endpoints will be analyzed using the curves of cumulative incidence., Start of protocol therapy to death without relapse/progression, assessed up to 2 years|Rate of acute GVHD, Will evaluate rate of acute GVHD of grades 2-4 and 3-4 by day 180 post-HCT. Documented/biopsy proven acute GVHD is graded according to Mount Sinai Acute Graft Versus Host Disease International Consortium Grading System. Time to event is measured from date of transplant to first documented/biopsy proven acute GVHD onset date. Acute GVHD will be censored at the time of last follow-up if patients remain alive and free of relapse/progression., Up to 180 days post hematopoietic cell transplantation (HCT)|Cumulative incidence of chronic GVHD, Will evaluate documented/biopsy proven chronic GVHD as scored according to National Institutes of Health Consensus Staging. Disease relapse/progression or NRM are considered competing risk events. Chronic GVHD will be censored at the time of last follow-up if patients remain alive and free of relapse/progression. Competing risks endpoints will be analyzed using the curves of cumulative incidence., Start of protocol therapy to documented/biopsy proven chronic GVHD, assessed up to 2 years|Ability to complete at least 7 cycles of revumenib therapy, Feasibility will be defined as ability to complete at least 7 cycles of revumenib therapy. Each cycle is 28 days., Up to 2 years|Cumulative incidence of infections, Up to 2 years