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

Phase 2

Not yet recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Azacitidine (AZA); Procedure: Allogeneic hematopoietic stem cell transplantation; Drug: Venetoclax

• Registration Number: NCT06903702
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-25
• Study First Submitted QC: 2025-03-25
• Status Verified: 2025-04
• Study First Posted: 2025-04-01
• Last Update Submitted: 2025-04-14
• Last Update Posted: 2025-04-15
• Study Start: 2025-04-30
• Primary Completion: 2027-03
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 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 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

• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
maintenance arm Azacitidine and Venetoclax (AZA/VEN)	Azacitidine (AZA)	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.
maintenance arm Azacitidine and Venetoclax (AZA/VEN)	Venetoclax	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.
Allogeneic hematopoietic stem cell transplantation (Allo-HCT arm)	Allogeneic hematopoietic stem cell transplantation	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.

Primary Outcome Measures

Name	Time	Method
1-year Relapse free survival (RFS)	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	3 years	will be defined with patients being alive and non-relapse mortality (NRM) will be defined as death in the absence of disease recurrence.

Trial Locations

Locations (7)

Memorial Sloan Kettering Cancer Center - Suffolk (Limited Protocol Activities); 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities); 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities); 🇺🇸 Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (Consent and Follow-up); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities); 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States