A Study of Azacitidine and Venetoclax in People With Acute Myeloid Leukemia (AML)

Launched by MEMORIAL SLOAN KETTERING CANCER CENTER · Jan 8, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating whether a combination of two medications, azacitidine and venetoclax, can effectively reduce or eliminate measurable residual disease (MRD) in adults with acute myeloid leukemia (AML). MRD refers to the small number of cancer cells that may remain after treatment and can lead to a return of the disease. The study specifically targets adults who have already undergone standard chemotherapy and are preparing for a stem cell transplant, which is a procedure that replaces the immune system with healthy cells from a donor.

To be eligible for this trial, participants must be at least 18 years old, have a confirmed diagnosis of AML, and have received two cycles of chemotherapy, achieving a certain level of remission. They should also have detectable MRD at a specific level. Throughout the trial, participants will receive the study medications and will be monitored closely for their health and response to treatment. It’s important for potential participants to understand that there are certain health conditions that may disqualify them from joining the study, so discussing eligibility with a healthcare provider is essential.

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ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Adult patient ≥18 years of age at the time of signing the informed consent form (ICF). Legal Authorized Representatives (LAR) are permitted.
• • 2. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
• • 3. Patient has a confirmed diagnosis of de-novo AML (non-APL) as per World Health Organization (2022) guidelines. All (non-APL) subtypes of AML are permitted, irrespective of ELN risk category or mutational status.
• • 4. Patient has received 2 cycles of intensive chemotherapy (either induction + consolidation or 2 induction cycles).
• • 5. 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.
• • 6. Patient and is either in CR, or CR with partial count recovery, either CRi/CRh\\\^1.
• • 1CR= 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 with ANC 500-1000 cells/µL and PLT 50,000-100,000 /µL. CRi = CR without meeting CRh criteria (residual neutropenia or thrombocytopenia).
• • 7. 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 CBF translocations) RT-qPCR at or above 0.01%, as described above (see section 3.6). If RT-qPCR is not available, MFC will be allowed for determining eligibility for molecular patients (at or above 0.1%).
• • 8. Patient is eligible for intensive chemotherapy and immediate allogeneic transplant, with intention to proceed to transplant after trial intervention.
• 9. Patient has an ECOG performance status of ≤3 10. Patient has adequate organ function defined as:
• • 1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• • 2. 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.
• • 3. Creatinine clearance greater than 30 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation.
• • 11. Absence of active uncontrolled infection, heart failure or severe psychiatric or neurological disease.
• • 12. 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.
• • 13. 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:
• • 1. Patients with acute promyelocytic leukemia (APL) or relapsed/refractory AML 2. Blast crisis of chronic myeloid leukemia 3. Patient with 5% blasts or more by flow or bone marrow aspirate differential (or IHC if no aspirate available) 4. Patient has received previous therapy with a venetoclax containing regimen. 5. 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.
• • 6. Patient has active uncontrolled systemic fungal, bacterial, or viral infection.
• • 7. Patient had recent, significant venous or arterial thrombotic event that would necessitate full anticoagulation or dual anti-platelet therapy, including 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 CHADS2 score below 4.
• • 8. Patient has mechanical heart valve. 9. Patient had recent significant hemorrhagic episode, at the discretion of investigator.
• • 10. Patient has significant active cardiac disease within 6 months prior to start of study treatment.
• • 11. Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• • 12. Female subject who is pregnant or lactating.