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A Study of Azacitidine and Venetoclax versus a Stem Cell Transplant in People 65 Years and Older with Acute Myeloid Leukemia
Trial Status: active
This phase II trial compares the effectiveness of azacitidine and venetoclax to a donor (allogeneic) stem cell transplant in treating patients 65 or older with acute myeloid leukemia (AML). Azacitidine works by switching off a protein called deoxyribonucleic acid methyltransferase. This action stops cancer cells from growing and dividing. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. An allogeneic stem cell transplant, sometimes called a bone marrow transplant, involves healthy stem cells from a donor that are infused into a patient. These stem cells may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. Giving azacitidine and venetoclax may be more effective than an allogeneic stem cell transplant in preventing AML from coming back in patients older than 65.
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 European LeukemiaNet (ELN) 2017 criteria
Treatment with azacitidine and venetoclax for the diagnosis of AML
* 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
Cardiac: Asymptomatic or if symptomatic, then left ventricular ejection fraction (LVEF) at rest must be > 40% and must improve with exercise
Creatinine clearance (CrCl) ≥ 50 ml/min (measured or calculated/estimated)
Pulmonary: Asymptomatic or if symptomatic, diffusion capacity of the lung for carbon monoxide (DLCO) > 50% of predicted (corrected for hemoglobin)
< 5 x upper limit of normal (ULN) liver function tests and < 2 x ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia
Karnosfsky performance status (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 absolute neutrophil count (ANC) > 1000 AND platelets (Plt) > 100K
* CR with partial hematological recovery (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 electronic case report form (eCRF)
History of prior allo-HCT
Patients who underwent prior leukemia directed treatment (other than aza/ven)
Patients with central nervous system (CNS) involvement at any time point prior to enrollment
Patients with previous exposure to venetoclax or an hypomethylating agent (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
Additional locations may be listed on ClinicalTrials.gov for NCT06903702.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Roni Tamari
Phone: 646-608-3738
PRIMARY OBJECTIVE:
I. Compare 1-year relapse free survival (RFS) in patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT) versus (vs) those treated with maintenance azacitidine and venetoclax (AZA/VEN) in older patients (65 years and older) with acute myeloid leukemia who achieve a measurable residual disease (MRD) negative complete remission (CR) or CR with incomplete hematologic recovery (CRi) after induction with 2 cycles of azacitidine and venetoclax.
SECONDARY OBJECTIVES:
I. Estimate overall survival (OS), duration of response and non-relapse mortality (NRM) among older patients with AML who are treated with allo-HCT vs maintenance AZA/VEN.
II. Assess health-related quality of life in patients treated with allo-HCT versus AZA/VEN maintenance. Assess treatment-related time toxicity in patients treated with allo-HCT versus AZA/VEN maintenance.
III. Compare the health care costs associated with maintenance AZA/VEN versus allo-HCT.
IV. Assess the impact of fitness, as measured by geriatric assessment, on outcomes.
EXPLORATORY OBJECTIVES:
I. Assess kinetics of MRD eradication and reappearance in patients on maintenance AZA/VEN versus allo-HCT by multiparameter flow cytometry and molecular testing.
II. Study genetic and immunologic determinants of relapse in patients who receive maintenance AZA/VEN versus allo-HCT.
OUTLINE: Patients who achieve CR or CRi, MRD negativity after 2 cycles of AZA/VEN are randomized to 1 of 2 arms.
ARM I: Starting 28-42 days after second cycle of standard of care (SOC) AZA/VEN, patients continue to receive azacitidine subcutaneously (SC) or intravenously (IV) once daily (QD) on days 1-7 and venetoclax orally (PO) QD on days 1-28. Cycles repeat every 28 days for up to 1 year (12 cycles) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography (ECHO) at pre-treatment and blood sample collection, and bone marrow aspiration and/or biopsy throughout the study.
ARM II: Starting 28-42 days after second cycle of SOC AZA/VEN, patients undergo allo-HCT. Additionally, patients undergo ECHO at pre-treatment and blood sample collection, and bone marrow aspiration and/or biopsy throughout the study.
After completion of study treatment, patients who received azacitidine and venetoclax are followed up at 30 days, and patients who received a stem cell transplant are followed up at 1, 3, 6, 9, and 12 and 13 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
