Revumenib, Azacitidine, and VENetoclax in Newly Diagnosed KMT2A-Rearranged AML (RAVEN)

This study is testing a new treatment combination called RAVEN, which includes revumenib, azacitidine, and venetoclax, in patients who are newly diagnosed with a specific type of acute myeloid leukemia (AML) called KMT2A- translocated AML.

People with this type of AML often have poor outcomes, so new treatments are needed that may work better and cause fewer side effects.

The study has two parts:

1. Induction Phase: Patients will receive treatment for up to 3 cycles. Each cycle lasts 28 days. The goal is to help the leukemia go into remission.
2. Continuation Phase: After remission and blood count recovery, patients will continue treatment until the leukemia returns, side effects become too severe, the patient receives a stem cell transplant, or another reason to stop treatment occurs.

Patients who receive an allogeneic stem cell transplant (stem cells from a donor) may also join a separate part of the study to test revumenib as maintenance treatment after transplant.

Study Overview

• Status: Not yet recruiting
• Conditions: Leukemia Acute Myeloid
• Intervention / Treatment: Drug: Azacitidine; Drug: Venetoclax; Drug: Revumenib

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lauren Higgins; Phone Number: 919-984-0000; Email: Lauren_Higgins@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Contact: Lauren Higgins; Phone Number: 919-984-0000; Email: Lauren_Higgins@med.unc.edu
      • Principal Investigator: Joshua Zeidner

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
• Age 18-65 years at the time of consent.
• Untreated AML based on 2022 WHO or ICC criteria with KMT2A translocation by local standard diagnostic testing by cytogenetics/karyotype or FISH

Exclusion Criteria:

• Isolated myeloid sarcoma (patients must have blood or marrow involvement with AML to enter study)
• Active central nervous system (CNS) involvement by AML. Of note, patients are eligible if CNS leukemia is in remission at the time of study entry.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KMT2A-translocated (KMT2Ar) acute myeloid leukemia (AML); Patients with KMT2A-translocated (KMT2Ar) acute myeloid leukemia (AML) did not receive a treatment.	Drug: Azacitidine; Subcutaneous or IV over 10-40 minutes on Days 1-7 or days 1-5, 8-9, in every 28 days, for 3 cycles.; Drug: Venetoclax; Per oral, daily in combination with posaconazole for 1- 28 days, for 3 cycles.; Drug: Revumenib; Per oral,12 hours in combination with posaconazole for 1- 28 days , for 3 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Complete remission (CR) rate will be determined as defined in the protocol Response Criteria. Bone marrow blasts < 5%; absence of circulating blasts; absence of extramedullary disease; ANC > 1.0 × 109/L (1,000/μL); platelet count ≥ 100 × 109/L (100 000/μL)	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete remission	Composite Complete remission (CCr) rate defined as complete remission (CR) + complete remission with incomplete recovery (CRi) + complete remission with partial hematologic recovery (CCr)= CR + CRi + CRh. CR: Bone marrow blasts < 5%; absence of circulating blasts; absence of extramedullary disease; ANC > 1.0 × 109/L (1,000/μL); platelet count ≥ 100 × 109/L (100 000/μL) CRi = All CR criteria except for residual neutropenia <1.0 × 109/L (1,000/μL) or thrombocytopenia < 100× 109/L (100 000/μL CRh: ANC ≥ 0.5 × 109/L (500/μL) and platelet count ≥50 × 109/L (50 000/μL), otherwise all other CR criteria met.	Up to 3 months
Duration of complete remission (DOCR)	Duration of complete remission (DOCR) will be defined as the time from the first complete remission to hematological relapse or death from any cause. CR: Bone marrow blasts < 5%; absence of circulating blasts; absence of extramedullary disease; ANC > 1.0 × 109/L (1,000/μL); platelet count ≥ 100 × 109/L (100 000/μL)	Up to 2 years
Event-free survival	Event-free survival will be determined as time until treatment failure (lack of CRc), relapse or death.	Up to 2 years
The number of treatment-emergent adverse events	The number of treatment-emergent special interest (AESIs) and serious adverse events (SAEs), and clinically significant test results will be submitted.	Up to 2 years
Relapse-free survival	Relapse-free survival will be determined as time to relapse or death after achieving CR.	Up to 2 years
Overall survival	Overall survival will be determined as time until date of death from any cause.	Up to 2 years
MRD-Negative (MRD<0.02%) complete remission	MRD-Negative (MRD<0.02%) complete remission rate will be assessed from bone marrow samples using Hematologics Flow MRD assay after 2 cycles of RAVEN treatment	Up to 3 months

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Joshua Zeidner, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: venetoclax; azacitidine; allogeneic stem cell transplant; revumenib
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax; revumenib
• Other Study ID Numbers: LCCC2508

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No