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

A Prospective, Single-Arm Study of Bugitinib Combined With Venetoclax and Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia (Non-M3)

This is a prospective, single-arm, exploratory study evaluating the combination of Bugitinib, Venetoclax, and Cytarabine in adult patients with relapsed or refractory acute myeloid leukemia (AML), excluding M3 subtype. The primary objective is to assess the rate of MRD (Minimal Residual Disease) negativity and the duration of MRD-negative status following treatment. Secondary objectives include evaluating overall response rate (CR/CRi), overall survival, progression-free survival, and safety. Treatment consists of induction therapy with Bugitinib and Venetoclax orally for 28 days combined with Cytarabine intravenously for 7-10 days per cycle. Patients who do not achieve complete remission after the first cycle may receive a second cycle with dose-adjusted Cytarabine. MRD and bone marrow assessments will guide therapy continuation, consolidation, or maintenance. Safety and tolerability will be closely monitored throughout the study.

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.