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A Study of Azacitidine and Venetoclax in People With Acute Myeloid Leukemia (AML)
Trial Status: active
This phase II trial tests how well azacitidine and venetoclax work to reduce measurable residual disease in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia (AML). Minimal residual disease (MRD) is when a small number of cancer cells from the bone marrow remain in the body during or after treatment. People with MRD have been shown to have a higher risk of cancer coming back after allogeneic stem cell transplant (relapse). Azacitidine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. 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. Giving azacitidine and venetoclax may reduce MRD in patients undergoing allogeneic stem cell transplantation for AML.
Inclusion Criteria
Adult patient ≥ 18 years of age at the time of signing the informed consent form (ICF). Legal authorized representatives (LAR) are permitted
Patient is willing and able to adhere to the study visit schedule and other protocol requirements
Patient has a confirmed diagnosis of de-novo AML (non-acute promyelocytic leukemia [APL]) as per World Health Organization (2022) guidelines. All (non-APL) subtypes of AML are permitted, irrespective of ELN risk category or mutational status
Patient has received 2 cycles of intensive chemotherapy (either induction + consolidation or 2 induction cycles)
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
Patient and is either in CR, or CR with partial count recovery, either CRi/CRh
* CR = Bone marrow (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 without meeting CRh criteria (residual neutropenia or thrombocytopenia)
* CRi = CR with ANC 500-1000 cells/µL and PLT 50,000-100,000 /µL
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 core binding factor [CBF] translocations) reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) at or above 0.01%, as described above. If RT-qPCR is not available, MFC will be allowed for determining eligibility for molecular patients (at or above 0.1%)
Patient is eligible for intensive chemotherapy and immediate allogeneic transplant, with intention to proceed to transplant after trial intervention
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limits of normal (ULN)
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
Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation
Absence of active uncontrolled infection, heart failure or severe psychiatric or neurological disease
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
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
Patients with acute promyelocytic leukemia (APL) or relapsed/refractory AML
Blast crisis of chronic myeloid leukemia
Patient with 5% blasts or more by flow or bone marrow aspirate differential (or immunohistochemistry [IHC] if no aspirate available)
Patient has received previous therapy with a venetoclax containing regimen
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
Patient has active uncontrolled systemic fungal, bacterial, or viral infection
Patient had recent, significant venous or arterial thrombotic event that would necessitate full anticoagulation or dual anti-platelet therapy, including pulmonary embolism (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 congestive heart failure, hypertension, age, diabetes mellitus, stroke (CHADS2) score below 4
Patient has mechanical heart valve
Patient had recent significant hemorrhagic episode, at the discretion of investigator
Patient has significant active cardiac disease within 6 months prior to start of study treatment
Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
Female subject who is pregnant or lactating
Additional locations may be listed on ClinicalTrials.gov for NCT06773208.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Eytan M. Stein
Phone: 646-608-3749
PRIMARY OBJECTIVE:
I. Determine the rate of MRD conversion from positive to negative post intervention.
SECONDARY OBJECTIVES:
I. Determine the degree of MRD decrease after intervention.
II. Determine percentage of patients with undetectable MRD after intervention.
III. Assess relapse free survival.
IV. Report incidence and severity of intervention-related adverse events (per Common Terminology Criteria for Adverse Events version 5 [CTCAE v.5]).
V. Assess intervention-related delay in transplant.
EXPLORATORY OBJECTIVES:
I. Assess correlation between primary outcome and AML European Leukemia Network (ELN) risk category.
II. Assess correlation between primary outcome and complete remission (CR)/ complete remission with incomplete bone marrow recovery (CRi)/complete remission with partial hematological recovery (CRh) at study entry.
III. Assess AML immune environment before and after intervention.
IV. Assess correlation between AML immune environment and MRD clearance.
V. Assess correlation between immune environment and relapse free survival.
OUTLINE:
Patients receive azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7 (Monday-Sunday) or days 1-5 (Monday-Friday, off Saturday-Sunday) and days 6-7 ( resume Monday-Tuesday) and venetoclax orally (PO) daily (QD) on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients then undergo allogeneic stem cell transplantation per standard of care. Additionally, patients may undergo bone marrow aspiration and biopsy throughout the trial.
After completion of study treatment, patients are followed up at 30 days and 1, 3, and 12 months post stem cell transplantation or end of treatment if stem cell transplantation did not take place.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center