NCT06177067

Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

A Phase 1 Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Refractory Acute Myeloid Leukemia
• Relapsed Acute Myeloid Leukemia
• Acute Leukemia of Ambiguous Lineage

Interventions

Type	Name	Description
DRUG	Revumenib	Given by mouth (capsule or liquid solution) or liquid solution by Nasogastric tube (NG) or Gastrostomy tube (G-tube)
DRUG	Venetoclax	Given by mouth (tablet) or by NG or G-tube
DRUG	Azacitidine	Given intravenously (IV) infusion
DRUG	intrathecal (IT) chemotherapy	Given intrathecal (IT)
DRUG	Cytarabine	Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.
DRUG	Methotrexate	Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.

Timeline

• Start date: 2024-04-19
• Primary completion: 2026-07-01
• Completion: 2027-04-01
• First posted: 2023-12-20
• Last updated: 2026-03-04

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study