Bugitinib Combined With Venetoclax and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia

Inclusion criteria

Participants must meet all of the following criteria:

• Age 18-70 years (inclusive), regardless of sex;
• Diagnosis of non-M3 acute myeloid leukemia (AML), and meeting at least one of the following conditions:

• Failure to achieve complete remission (CR) after standard induction chemotherapy;
• First CR duration ≤12 months;
• First CR duration >12 months, followed by relapse and failure of at least one line of standard chemotherapy;
• Relapsed disease after ≥2 prior lines of therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Estimated life expectancy ≥3 months;
• Adequate organ function, defined as:

• Cardiac: left ventricular ejection fraction (LVEF) ≥50% by echocardiography, with no clinically significant ECG abnormalities;
• Renal: serum creatinine ≤2.0 × upper limit of normal (ULN) and creatinine clearance ≥60 mL/min (Cockcroft-Gault);
• Hepatic: ALT and AST ≤3.0 × ULN;
• Total bilirubin ≤2.0 × ULN (≤3.0 × ULN for patients with Gilbert syndrome);
• Oxygen saturation ≥92% on room air;
• Ability to take oral medications and comply with study procedures;
• Willingness to participate and provide written informed consent.

Exclusion criteria

Participants meeting any of the following criteria will be excluded:

• Known hypersensitivity to any study drug or its excipients;
• Active central nervous system (CNS) leukemia (patients with prior CNS involvement who achieved complete remission and are clinically stable may be eligible);
• Active, uncontrolled bacterial, viral, or systemic fungal infection;
• Known hereditary bleeding or coagulation disorders, history of non-traumatic bleeding or thromboembolism, or other conditions that may increase bleeding risk;
• Evidence of active infection, including:

• Hepatitis B virus (HBV) infection with positive HBsAg or HBcAb and HBV DNA >100 copies/mL;
• Hepatitis C virus (HCV) antibody positive with detectable HCV RNA;
• Human immunodeficiency virus (HIV) infection;
• Positive test for syphilis;
• Active bleeding or clinically significant bleeding tendency, including but not limited to:

• Active gastrointestinal bleeding, intracranial hemorrhage, or bleeding in other vital organs;
• Grade ≥3 bleeding event within 4 weeks prior to enrollment (per CTCAE);
• Known hereditary bleeding disorders (e.g., hemophilia);
• Severe platelet dysfunction not correctable;
• Significant cardiovascular disease, including but not limited to:

• New York Heart Association (NYHA) class III-IV heart failure;
• Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to enrollment;
• Clinically significant ventricular arrhythmias or unexplained syncope (excluding vasovagal or dehydration-related causes);
• Severe cardiomyopathy;
• History of or concurrent other malignancies (except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix);
• Clinically significant central nervous system disorders (e.g., epilepsy, stroke, psychiatric disorders) that may affect compliance or safety;
• Participation in another interventional clinical trial within 30 days prior to enrollment;
• Pregnant or breastfeeding women, or subjects planning pregnancy during the study period or within 6 months after the last dose and unwilling to use effective contraception;
• Known or suspected drug abuse or alcohol dependence;
• Requirement for concomitant use of strong CYP3A inhibitors or inducers that cannot be discontinued or dose-adjusted per protocol;
• Any other condition that, in the investigator's opinion, would make the subject unsuitable for participation.