Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
Start Date
4/19/2024
Completion Date
4/1/2027
Summary
This is a research study to find out if adding a new study drug called revumenib to commonly used chemotherapy drugs is safe and if they have beneficial effects in treating patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that did not go into remission after treatment (refractory) or has come back after treatment (relapsed), and to determine the total dose of the 3-drug combination of revumenib, azacitidine and venetoclax that can be given safely in participants also taking an anti-fungal drug. Primary Objective * To determine the safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives * Describe the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and overall survival for patients treated with revumenib + azacitidine + venetoclax at the recommended phase 2 dose (RP2D).
Detailed Description
Patients will receive revumenib + azacitidine + venetoclax in a dose-escalation fashion. The protocol starts at dose level 1. If there are no dose limiting toxicities at dose level 1, then patients will be treated at dose level 2, which equates to the dose of revumenib increasing from 65 to 95 mg/m\^2 while the venetoclax exposure remains the same at 21 days. Alternatively, if there are dose limiting toxicities at dose level 1, then the dose level will be deescalated to dose level -1, which equates to the length of exposure of venetoclax being decreased from 21 days to 14 days, while the dose of revumenib stays at 65 mg/m\^2. The doses of azacitidine will remain constant at all dose levels. For patients whose primary physician considers that single agent revumenib is beneficial (e.g., transition to hematopoietic cell transplant), revumenib can be continued after discussing with study principal investigator. Patients who undergo HCT will be taken off therapy at the time of HCT, but will remain on study. Post-transplant therapy will be determined by the HCT physician. Patients who do not go on to receive an HCT, may continue to receive revumenib, venetoclax and azacitidine as long as their primary physician considers it beneficial and there are no unacceptable side effects.
Eligibility Criteria
Age Range: 1 years to 30 years
Interventions
Revumenib
Venetoclax
Azacitidine
intrathecal (IT) chemotherapy
Cytarabine
Methotrexate
Conditions
Locations
Rady Children's Hospital
San Diego, California 92132
United States
Children's Hospital Colorado
Aurora, Colorado 80045
United States
Children's Healthcare of Atlanta
Atlanta, Georgia 30329
United States
Children's Mercy Hospital of Kansas City
Kansas City, Missouri 64108
United States
Memorial Sloan- Kettering Cancer Center
New York, New York 10065
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States
St. Jude Children's Research Hospital
Memphis, Tennessee 38105
United States
UT Southwestern/Simmons Cancer Center
Dallas, Texas 75390
United States
Cook Children's Medical Center
Fort Worth, Texas 76104
United States