A Study of Azacitidine and Venetoclax Versus a Stem Cell Transplant in People 65 Years and Older With Acute Myeloid Leukemia

NCT06903702 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 25-063
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief Summary

The researchers are doing this study to find out if an allogeneic hematopoietic stem cell transplant (HSCT) or maintenance therapy with azacitidine and venetoclax is more effective at keeping AML from coming back (relapsing).

Conditions

Acute Myeloid Leukemia

Keywords

Azacitidine; Venetoclax; Allogeneic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• 1-year Relapse free survival (RFS)

  Relapse free survival (RFS)- will be defined with patients being alive and without any evidence of disease. i.e. no morphologic relapse and no emergence of minimal residual disease. In the event of emergence of MRD without a morphologic relapse, this will be defined as relapse only if documented on 2 separate time points. For patients alive and in remission at the data cut-off, RFS will be censored at the last assessment date.

  1 year

Secondary Outcomes (1)

• Overall survival (OS)

  3 years

Study Arms (2)

maintenance arm Azacitidine and Venetoclax (AZA/VEN)

EXPERIMENTAL

Patients randomized to the maintenance arm (AZA/VEN) will be treated with azacitidine given daily for 7 days starting on Day 1 of each Cycle (7 consecutive days or a total of 7 days with a 2 day break due to weekends or holidays is permissible). Venetoclax will be taken orally daily for 28 days. A cycle will be considered 28 days.

Drug: Azacitidine (AZA); Drug: Venetoclax

Allogeneic hematopoietic stem cell transplantation (Allo-HCT arm)

EXPERIMENTAL

Patients who are randomized to the transplant arm will start the conditioning regimen no later than 6 weeks (day 42) after C2D1 of AZA/VEN.

Procedure: Allogeneic hematopoietic stem cell transplantation

Interventions

Azacitidine (AZA) DRUG

given daily for 7 days starting on Day 1 of each Cycle

maintenance arm Azacitidine and Venetoclax (AZA/VEN)

Venetoclax DRUG

orally daily for 28 days

maintenance arm Azacitidine and Venetoclax (AZA/VEN)

Allogeneic hematopoietic stem cell transplantation PROCEDURE

After the conditioning treatment, the HSCT procedure is part of standard care on Day 0.

Allogeneic hematopoietic stem cell transplantation (Allo-HCT arm)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Adult patients ≥65 years of age at the time of signing the informed consent form.
• Confirmed diagnosis of acute myeloid leukemia according to the ELN 2017 criteria
• Treatment with azacitidine and venetoclax for the diagnosis of AML
• o The first cycle of study treatment will start 28-42 days after the start of the second cycle of SOC AZA/VEN. In the event that patients can't be admitted for allo-HCT until after Day 42 due to donor related issues, an additional cycle of AZA/VEN will be allowed as a bridge to the transplant, and then initiation of conditioning will start no later than day 42 after the start of the third cycle.
• Patients with adequate organ function to be considered as candidates for allo-HCT:
• Cardiac: asymptomatic or if symptomatic, then LVEF at rest must be \>40% and must improve with exercise.
• Renal: CrCl ≥50 ml/min (measured or calculated/estimated).
• Pulmonary: asymptomatic or if symptomatic, DLCO \> 50% of predicted (corrected for hemoglobin)
• Hepatic: \< 5x ULN liver function tests and \< 2x ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
• KPS of ≥ 70
• Patients with suitable donor for allo-HCT
• Patients must achieve a morphologic remission \<5% blast with MRD negative status by flow cytometry (defined as one or less residual leukemic blasts per 1000 leukocytes (or 10\^3)) meeting one of the below:
• Complete remission (CR) defined as: \<5% blasts with ANC\> 1000 AND Plt \>100K
• CRh defined as \<5% blasts with ANC \> 500 AND Plt \>50K
• CRi defined as \<5% blasts with ANC\< 1000 OR Plt \< 100K

You may not qualify if:

• Patients who are not considered to be transplant eligible (either due to lack of suitable donor or due to comorbidities/performance status). The reason the patient is not considered transplant eligible will be documented in the eCRF.
• History of prior allo-HCT
• Patients who underwent prior leukemia directed treatment (other than aza/ven)
• Patients with CNS involvement at any time point prior to enrollment.
• Patients with previous exposure to venetoclax or an HMA for the treatment of a myeloid malignancy
• Patients who are planned for treatment other than AZA/VEN
• Patients who are planned for treatment with HMA/VEN with another agent (e.g. a "triplet")
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Consent and Follow-up)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Suffolk (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Roni Tamari, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roni Tamari, MD

CONTACT

646-608-3738; ABMTTrials@mskcc.org

Eytan Stein, MD

CONTACT

646-608-3749

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, multi-center, open label, phase II study .

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (7)