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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Given by mouth (capsule or liquid solution) or liquid solution by Nasogastric tube (NG) or Gastrostomy tube (G-tube)
Given by mouth (tablet) or by NG or G-tube
Given intravenously (IV) infusion
Given intrathecal (IT)
Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.
Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.
Rady Children's Hospital
San Diego, California, United States
RECRUITINGChildren's Hospital Colorado
Aurora, Colorado, United States
RECRUITINGChildren's Mercy Hospital of Kansas City
Kansas City, Missouri, United States
RECRUITINGMemorial Sloan- Kettering Cancer Center
New York, New York, United States
RECRUITINGCincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
RECRUITINGChildren's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
RECRUITINGSt. Jude Children's Research Hospital
Memphis, Tennessee, United States
RECRUITINGUT Southwestern/Simmons Cancer Center
Dallas, Texas, United States
RECRUITINGCook Children's Medical Center
Fort Worth, Texas, United States
RECRUITINGThe safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL
The primary endpoint is the recommended phase 2 dose (RP2D) of revumenib + azacitidine + venetoclax.
Time frame: 43 days from the start of therapy.
The rates of complete remission (CR)
CR is defined as bone marrow with \< 5% blasts confirmed by flow cytometry, ANC ≥500/μL and platelets ≥50,000/μL without transfusions, and no evidence of extramedullary disease.
Time frame: 43 days from the start of therapy
The rates of complete remission with incomplete count recovery (CRi)
CRi is defined as bone marrow with \<5% blasts confirmed by flow cytometry and ANC \<500/μL or platelets \<50,000/μL without transfusions
Time frame: 43 days from the start of therapy
The overall survival of patients treated at the RP2D.
Kaplan-Meier estimates with 95% confidence intervals will be used to describe overall survival.
Time frame: 1 year
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