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

May 1, 2026 updated by: St. Jude Children's Research Hospital

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92132
        • Recruiting
        • Rady Children's Hospital
        • Principal Investigator:
          • Dennis Kuo, MD
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado
        • Contact:
        • Principal Investigator:
          • Kelly Faulk, MD
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Children's Healthcare of Atlanta
        • Contact:
        • Principal Investigator:
          • Himalee Sabnis, MD
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospital of Kansas City
        • Principal Investigator:
          • Keith August, MD
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan- Kettering Cancer Center
        • Contact:
        • Principal Investigator:
          • Maria-Luisa Sulis, MD
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Lauren Pommert, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Principal Investigator:
          • Sarah Tasian, MD
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Recruiting
        • St. Jude Children's Research Hospital
        • Principal Investigator:
          • Hiroto Inaba, MD, PhD
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center
        • Principal Investigator:
          • Kathleen Ludwig, MD
        • Contact:
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • Cook Children's Medical Center
        • Principal Investigator:
          • Holly Pacenta, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria: Participants must have a diagnosis of AML or ALAL and meet the criteria below:

  • Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.

However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.

  • Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214
  • Adequate organ function, defined as total bilirubin < 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin <3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m^2, and left ventricular ejection fraction ≥ 40%
  • QTcF < 480 msec (average of triplicate)
  • Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
  • Lansky ≥ 60 for patients who are < 16 years old and Karnofsky ≥ 60% for patients who are > 16 years old.
  • At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m^2/day). In addition, all toxicities must have resolved to grade 1 or less.
  • Patients must have a leukocyte count <25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
  • For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
  • Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
  • Patients of reproductive potential must agree to use effective contraception for the duration of study participation.

Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.

Exclusion Criteria:

  • Patients who are pregnant or breastfeeding are not eligible.
  • Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
  • Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All Eligible Participants

All eligible patients receive the following intervention:

Revumenib, Venetoclax, Azacitidine, Intrathecal chemotherapy
Drug: Revumenib
Given by mouth (capsule or liquid solution) or liquid solution by Nasogastric tube (NG) or Gastrostomy tube (G-tube)
Other Names:
  • SNDX-5613
Drug: Azacitidine
Given intravenously (IV) infusion
Other Names:
  • 5-azacitidine
  • VIDAZA®
Drug: intrathecal (IT) chemotherapy
Given intrathecal (IT)
Other Names:
  • ITMHA
  • methotrexate/hydrocortisone/cytarabine
Drug: Cytarabine
Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.
Other Names:
  • Ara-C
  • Cytosar®
Drug: Methotrexate
Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.
Other Names:
  • MTX
  • Trexall®
Drug: Venetoclax
Given by mouth (tablet) or by NG or G-tube
Other Names:
  • Venclextra®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL
Time Frame: 43 days from the start of therapy.
The primary endpoint is the recommended phase 2 dose (RP2D) of revumenib + azacitidine + venetoclax.
43 days from the start of therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rates of complete remission (CR)
Time Frame: 43 days from the start of therapy
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.
43 days from the start of therapy
The rates of complete remission with incomplete count recovery (CRi)
Time Frame: 43 days from the start of therapy
CRi is defined as bone marrow with <5% blasts confirmed by flow cytometry and ANC <500/μL or platelets <50,000/μL without transfusions
43 days from the start of therapy
The overall survival of patients treated at the RP2D.
Time Frame: 1 year
Kaplan-Meier estimates with 95% confidence intervals will be used to describe overall survival.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Collaborators

Syndax Pharmaceuticals

Investigators

  • Principal Investigator: Hiroto Inaba, MD, PhD, St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 19, 2024

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

December 11, 2023

First Submitted That Met QC Criteria

December 11, 2023

First Posted (Actual)

December 20, 2023

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RAVAML
  • NCI-2023-10509 (Registry Identifier: NCI Clinical Trial Registration Program)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

IPD Sharing Time Frame

Data will be made available at the time of article publication.

IPD Sharing Access Criteria

Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Refractory Acute Myeloid Leukemia

Clinical Trials on Revumenib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sweden

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe