Exploratory Study of Venetoclax, Homoharringtonine, Azacitidine Plus G-CSF for Newly Diagnosed AML (VHAG)

Prior treatment

• History of prior myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, myelofibrosis, etc.
• Prior receipt of hypomethylating agents, venetoclax (VEN), or systemic chemotherapy for myelodysplastic syndromes (MDS).
• Prior receipt of any investigational drug or device therapy for MDS/AML.
• Concurrent participation in another clinical trial.
• Ingestion of grapefruit, grapefruit juice, Seville oranges, star fruit, or their products within 72 hours prior to the first dose.
• Presence of a second malignancy within 2 years prior to enrollment, excluding cured carcinoma in situ of the cervix or breast, completely resected basal cell carcinoma or localized squamous cell carcinoma of the skin, or localized malignancies cured by surgery and requiring no further follow-up.

Other illness

• Positive HIV antibody during the screening period.
• Positive HBsAg or HCV antibody with a high-sensitivity viral load above the lower limit of detection within 3 months (excluding those who are cured or with persistent low-level replication).
• Chronic respiratory failure requiring long-term oxygen therapy.
• Presence of severe cardiac, hepatic, renal, endocrine, metabolic, immune, neurological, or psychiatric disorders.
• History of hypersensitivity to the study drug (including azacitidine excipients).
• Impaired drug absorption due to malabsorption syndrome, short bowel syndrome, or other conditions affecting oral drug absorption.
• Active tuberculosis or other severe infections requiring intravenous anti-infective therapy for ≥7 days.

Other

• Acute promyelocytic leukemia (APL).
• AML with central nervous system (CNS) involvement confirmed by imaging or cerebrospinal fluid examination.
• The investigator judges that the patient is otherwise ineligible to participate in this study.

• The patient has fully understood the study, voluntarily participated, and signed the informed consent form (ICF).
• Newly diagnosed acute myeloid leukemia (AML) confirmed by bone marrow morphology, immunophenotyping, cytogenetics, and/or molecular biology testing, in accordance with the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2022 edition).
• No prior systemic therapy for AML (including induction, consolidation, or maintenance therapy).
• Patients judged unfit for standard cytarabine plus anthracycline induction chemotherapy due to age or comorbidities.
• Short-term use of hydroxyurea or low-dose cytarabine before enrollment to control hyperleukocytosis is permitted.
• Age ≥ 75 years, or age 18-74 years with any of the following comorbidities:
• ECOG performance status 2-3
• History of congestive heart failure, left ventricular ejection fraction (LVEF) ≤ 50%, or chronic stable angina
• Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% predicted, or forced expiratory volume in 1 second (FEV1) ≤ 65% predicted
• Creatinine clearance 30-45 mL/min (≥ 30 and \< 45)
• Moderate hepatic impairment: total bilirubin \> 1.5 × ULN and ≤ 3 × ULN
• Other comorbidities deemed unfit for standard chemotherapy by the investigator
• Estimated survival time ≥ 12 weeks.
• For patients aged ≥ 75 years: ECOG performance status 0-2.
• For patients aged 18-74 years: ECOG performance status 0-3.
• Creatinine clearance ≥ 30 mL/min (calculated by the Cockcroft-Gault formula).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × ULN; may be relaxed to ≤ 3 × ULN in patients with leukemic hepatic infiltration.
• For patients \< 75 years old, total bilirubin ≤ 3 × ULN.