Venetoclax-Decitabine in Untreated Elderly/Unfit AML

Prior treatment

• Previously treated AML patients (received prior induction chemotherapy, regardless of response).
• Secondary AML, including:Therapy-related AML (per WHO classification)、AML with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN)
• Use of strong/moderate CYP3A4 inducers within 3 days prior to treatment initiation.
• Active cardiac disease, defined as ≥1 of the following:Myocardial infarction within 6 months before enrollment；History of symptomatic arrhythmia requiring medication；Uncontrolled/symptomatic congestive heart failure (NYHA Class \>2)

Other illness

• Hypersensitivity to any study drugs.
• Active malignancy in other organs (requiring treatment).
• Active infections, including:Untreated tuberculosis or pulmonary aspergillosis
  • Known HIV, active hepatitis B (HBV), or hepatitis C (HCV)
• Medical history of:Epilepsy requiring medication、Dementia or psychiatric disorders impairing protocol compliance
• Conditions limiting oral drug absorption (e.g., malabsorption syndrome).

Lab values

• Concurrent hematologic disorders (e.g., hemophilia, myelofibrosis, or other conditions deemed ineligible by the investigator). Exception: Patients with prior blood count abnormalities but confirmed non-MDS/MPN by bone marrow examination may be included.

Other

• AML with BCR::ABL1 fusion or chronic myeloid leukemia (CML) in blast crisis.
• Pregnant or lactating women.
• Clinically significant hepatic/renal dysfunction exceeding inclusion criteria limits.
• Central nervous system (CNS) leukemia at baseline.
• Investigator's discretion for ineligibility.

• Patients meeting the World Health Organization (WHO) 2022 diagnostic criteria for acute myeloid leukemia (AML), excluding:Acute promyelocytic leukemia (APL)
  • AML with recurrent genetic abnormalities, including:t(8;21)(RUNX1::RUNX1T1)
  • inv(16)(p13.1q22) or t(16;16)(p13.1q22)/CBFβ::MYH11
• Patients classified as AML, not otherwise specified (NOS) per WHO criteria, excluding:Acute panmyelosis with myelofibrosis 、Myeloid sarcoma
• Age and fitness criteria:
  • -Group A: Age ≥65 years (unwilling to receive intensive chemotherapy)
  • Group B: Age \>18 years and ineligible for standard-dose chemotherapy, defined by ≥1 of the following:ECOG performance status 2 or 3；History of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% DLCO ≤65% or FEV1 ≤65%Creatinine clearance ≥30 mL/min but ≤45 mL/min (Cockcroft-Gault or 24-hour urine collection)、Any other condition deemed incompatible with standard chemotherapy (requires PI approval)
• No prior AML therapy, except:Hydroxyurea、Low-dose cytarabine (\<1.0 g/day)
• ECOG performance status ≤3
• Laboratory requirements (within 7 days prior to treatment):AST/ALT/ALP ≤3×ULN (≤5×ULN if due to leukemic involvement)、Total bilirubin ≤2×ULN、Cardiac enzymes \<2×ULN、Serum creatinine clearance ≥30 mL/min (measured or calculated)
• Contraception requirements:Negative pregnancy test (within 72 hours before treatment) for women of childbearing potential；Agreement to use effective contraception during treatment and for 3 years after therapy
• Life expectancy ≥2 months
• Informed consent:Signed by patient, legal guardian, or immediate family member (if patient is unable to consent due to medical condition)