A Study of Azacitidine and Venetoclax in People With Acute Myeloid Leukemia (AML)

A Phase 2 Study of Azacitidine and Venetoclax to Treat Acute Myeloid Leukemia Patients With Measurable Residual Disease Before an Allogeneic Stem Cell Transplant

The purpose of this study is to find out if azacitidine and venetoclax are an effective treatment approach to get rid of or lower measurable residual disease (MRD) in people with acute myeloid leukemia (AML) who have received standard chemotherapy and are planning to have an allogeneic hematopoietic stem cell transplant (HSCT). Allogeneic HSCT, sometimes called a bone marrow transplant, involves receiving healthy blood-forming cells (stem cells) from a donor in order to replace the patient's immune system and lower the chances of the disease returning (relapse).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Azacitidine (AZC); Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eytan Stein, MD; Phone Number: 646-608-3749; Email: steine@mskcc.org
• Study Contact Backup: Name: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982; Email: yisraem@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All protocol activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All protocol Activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All Protocol Activities)
      • Contact: Meira Yisraeli Salman, MD; Phone Number: 646-608-3982

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Adult patient ≥18 years of age at the time of signing the informed consent form (ICF). Legal Authorized Representatives (LAR) are permitted.

  2. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.

  3. Patient has a confirmed diagnosis of de-novo AML (non-APL) as per World Health Organization (2022) guidelines. All (non-APL) subtypes of AML are permitted, irrespective of ELN risk category or mutational status.

  4. Patient has received 1-3 cycles of intensive chemotherapy for remission induction.

  5. Patient is in a morphologic remission, defined as less than 5% percent blasts seen by aspirate differential (or immunohistochemistry if no aspirate available) from bone marrow biopsy.

  6. Patient and is either in CR, or CR with partial count recovery, either CRi/CRh\^1.

  1CR= BM with <5% blasts, absence of circulating blasts; absence of extramedullary disease, absolute neutrophil count (ANC) ≥ 1000 cells/µL and platelet (PLT) count ≥ 100,000/µL. CRh = CR with ANC 500-1000 cells/µL and PLT 50,000-100,000 /µL. CRi = CR without meeting CRh criteria (residual neutropenia or thrombocytopenia).

  7. Patient has positive measurable residual disease (MRD) at or above a level of 0.1%, by flow cytometry (MFC) or in molecular cases (NPM1 mutated or one of the CBF translocations) RT-qPCR at or above 0.01%, as described above (see section 3.6). If RT-qPCR is not available, MFC will be allowed for determining eligibility for molecular patients (at or above 0.1%).

  8. Patient is eligible for intensive chemotherapy and immediate allogeneic transplant, with intention to proceed to transplant after trial intervention.

  9. Patient has an ECOG performance status of ≤3 10. Patient has adequate organ function defined as:

  1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  2. Serum total bilirubin < 1.5 x ULN (or direct bilirubin normal in subjects with total bilirubin > 1.5 ULN). Except in cases of Gilbert's disease.

  3. Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.

     11. Absence of active uncontrolled infection, heart failure or severe psychiatric or neurological disease.

     12. Females of childbearing potential may participate provided they have a negative serum pregnancy test at screening and a negative serum OR urine pregnancy test within two weeks of starting on treatment.

     13. Females of reproductive potential should use effective contraception during the study, and for 6 months after last dose of azacitidine. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after.

     Exclusion Criteria:

     1. Patients with acute promyelocytic leukemia (APL) or relapsed/refractory AML 2. Blast crisis of chronic myeloid leukemia 3. Patient with 5% blasts or more by bone marrow aspirate differential (or IHC if no aspirate available) 4. Patient has received previous therapy with a venetoclax containing regimen. 5. Patient has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.

     6. Patient has active uncontrolled systemic fungal, bacterial, or viral infection.

     7. Patient had recent, significant venous or arterial thrombotic event that would necessitate full anticoagulation or dual anti-platelet therapy, including PE within 30 days prior to start of treatment or insertion of drug eluting stent within 6 months prior to start of treatment. Chronic indications for anticoagulation such as atrial fibrillation, can be included if CHADS2 score below 4.

     8. Patient has mechanical heart valve. 9. Patient had recent significant hemorrhagic episode, at the discretion of investigator.

     10. Patient has significant active cardiac disease within 6 months prior to start of study treatment.

     11. Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.

     12. Female subject who is pregnant or lactating.

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: Azacitidine and Venetoclax; Cycle length: 28 days Azacitidine 75 mg/m2 daily, on days 1-7, given IV or SC (generally given IV in our institution) Venetoclax 400 mg orally daily on days 1-28	Drug: Azacitidine (AZC); 75 mg/m2 daily, on days 1-7, given IV or SC; Drug: Venetoclax; Venetoclax 400 mg orally daily on days 1-28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of MRD conversion	MRD status will be assessed from end-of-cycle bone marrow aspirate, in all patients. MRD will be assessed by flow cytometry (MFC) or by RT-qPCR in molecular patients. This is a dichotomous variable of positive versus negative MRD, with a pre-defined threshold as described above, of 0.1% for MFC or 0.01% in molecular patients .	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
degree of MRD decrease	will be summarized as median and interquartile range.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Eytan Stein, MD, Memorial Sloan Kettering Cancer Center; Principal Investigator: Meira Yisraeli Salman, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Venetoclax; Azacitidine; Allogeneic Stem Cell Transplant; 24-347
• 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
• Other Study ID Numbers: 24-347

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

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