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

A Randomized, Multicenter, Phase II Study of Maintenance Azacitidine and Venetoclax Versus an Allogeneic Stem Cell Transplant in Older Patients (65 Years and Older) With Acute Myeloid Leukemia Who Achieve an MRD Negative Complete Remission After Induction With Azacitidine and Venetoclax

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).

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 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

• 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.