VA-CIG Regimen for Previously Untreated Acute Myeloid Leukemia: A Multicenter Prospective Single-Arm Trial

A Multicenter, Prospective, Single-Arm Clinical Trial of Venetoclax in Combination With Azacitidine, Cytarabine, Idarubicin and G-CSF (VA-CIG) for Patients With Previously Untreated Acute Myeloid Leukemia

This is a multicenter, prospective, single-arm clinical study designed to evaluate the efficacy and safety of the VA-CIG regimen (venetoclax combined with azacitidine, idarubicin, low-dose cytarabine and granulocyte colony-stimulating factor [G-CSF]) as induction therapy for previously untreated patients with fit acute myeloid leukemia (AML) who are eligible for intensive chemotherapy. This study aims to evaluate the efficacy and safety of the VA-CIG regimen in the target patient population.

Inclusion Criteria:

• Diagnosis of acute myeloid leukemia (AML, excluding acute promyelocytic leukemia) confirmed by morphology, immunophenotyping and molecular genetics, in accordance with the WHO 2022 diagnostic criteria for AML;
• Age 18-70 years, with no gender restriction;
• No prior AML-related treatment has been received; exceptions are made for the use of hydroxyurea or similar agents during the diagnostic screening phase to control peripheral blood leukemic blasts;
• Patients must be assessed as tolerable to intensive chemotherapy regimens; evaluation of tolerance to intensive chemotherapy shall be performed in accordance with the Ferrara 2013 criteria (Appendix A);
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
• Serum creatinine ≤ 2.0 × upper limit of normal (ULN), or creatinine clearance > 40 mL/min calculated by the Cockcroft-Gault formula for glomerular filtration rate (GFR);
• Total bilirubin ≤ 2 × ULN, and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 × ULN;
• Left ventricular ejection fraction (LVEF) ≥ 45%, or LVEF measured by echocardiography (ECHO) within the normal range;
• Expected survival > 3 months.

Exclusion Criteria:

• Subjects with a history of myeloproliferative neoplasms (MPNs), including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, and acute myeloid leukemia (AML) with BCR-ABL1 translocation;
• Patients with a prior history of venetoclax or azacitidine (Aza) treatment for other diseases;
• Known hypersensitivity to any component of the investigational medicinal products;
• History of other concurrent malignancies within 2 years prior to enrollment, except:

Adequately treated carcinoma in situ of the cervix or breast; Basal cell carcinoma or localized squamous cell carcinoma of the skin; Previously controlled malignancies treated with radical surgical resection (or other curative modalities), etc.

• Presence of uncontrolled severe infection or active bleeding;
• Pregnant or lactating women;
• Subjects with active, treatment-uncontrolled viral infection caused by HIV, hepatitis B virus, or hepatitis C virus;
• Subjects with evidence of central nervous system leukemia before treatment initiation;
• Women of childbearing potential who do not agree to use at least one reliable contraceptive method from Day 1 of the study until 90 days after the last dose of study medication; sexually active male subjects who do not agree to use contraceptive measures from Day 1 of the study until 90 days after the last dose of study medication; male subjects who do not agree to refrain from sperm donation from the start of study drug administration until at least 90 days after the last dose;
• Subjects with epilepsy requiring pharmacotherapy, dementia, or other abnormal psychiatric conditions that impair the ability to understand or comply with the study protocol;
• Presence of psychiatric disorders or cognitive impairment that prevents cooperation with treatment and follow-up; conditions limiting oral drug intake or gastrointestinal absorption.