Discontinuation of Hypomethylating Agent and Venetoclax in Patients With AML MRD

Inclusion Criteria:

• Adults 18 years of age or older at the time of obtaining informed consent.

• Diagnosed with Acute Myeloid Leukemia (AML) (non-M3) as defined by 2016 World HealthOrganization (WHO)

• Eastern Cooperative Group (ECOG) performance status score ≤ 2

• Currently on frontline therapy with HMA (azacitidine or decitabine)/VEN and achievedComplete Remission (CR)/Complete Remission with incomplete marrow recovery (CRi)with MRD negativity defined as < 0.1% by Multiparameter Flow Cytometry (MFC)

• Within 12 months of starting HMA (azacitidine or decitabine)/VEN

• Ineligible for or declined allogeneic hematopoietic cell transplantation (HCT)

• Ability to understand and the willingness to sign a written informed consentdocument

• Must agree to adhere to the study visit schedule and other protocol requirements

• Patients must be able to provide adequate Bone Marrow (BM) aspirate and biopsyspecimens for histopathological and Measurable Residual Disease analysis during thescreening procedure

Exclusion Criteria:

• Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that arenot commercially available) for the treatment of AML within 28 days, or 5half-lives, at the start of the study. Only patients who are receiving frontline HMA (azacitidine or decitabine)/VEN are potentially eligible, but if they had received acourse of hydroxyurea prior to achieving CR/CRi, this is allowed.

• Any serious medical condition or uncontrolled current illness including, but notlimited to ongoing or active infection, symptomatic congestive heart failure,unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/socialsituations that would limit compliance with study requirements or will place thesubject at unacceptable risk if he/she participates in the study. Controlledinfections or other medical conditions on long-term therapy is allowed.

• Patients who harbored TP53 mutation at diagnosis

• AML with extramedullary involvement including central nervous system (CNS)involvement, myeloid sarcoma, and leukemia cutis requiring directed therapy at thetime of enrollment.

• Patient is pregnant.