CLAG+VEN vs CLAG in the Treatment of Relapsed/Refractory AML

The efficacy and prognosis of relapsed/refractory(r/r) AML are very poor, and there is no standard chemotherapy regimen were defined for r/r AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells. Previous studies have confirmed the efficacy of cladribine in the treatment of r/r AML, with a response rate of 30-45%.Our previous experience has shown that CLAG in combination of venetoclax are effective with tolerable toxicity profiling. However, there is a lack of multicenter, prospective, randomized controlled trials to further confirm the results. Therefore, a clinical study is planned to evaluate the efficacy and safety of CLAG+VEN compared to CLAG in r/r AML who were eligible for intensive therapy.

Inclusion criteria

• Diagnosed of AML according to the World Health Organization (WHO) classification.
• All patients should aged 18 to 65 years.
• Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
• Diagnostic criteria for relapsed AML: Leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) after CR, or leukemia cell infiltration appears outside the marrow.
• Diagnostic criteria for refractory AML: The newly diagnosed patients who failed to respond to two courses of standard treatment; Patients who relapsed within 12 months after consolidation intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia.
• The score of Eastern Cooperative Oncology Group (ECOG) is 0-2.
• Renal function: creatinine clearance rate ≥ 30ml/min.
• Liver function: ALT<5 times normal value, bilirubin<3 times normal value.
• Predicted survival ≥ 3 months.
• Able to accept oral Venetoclax.
• Sign an informed consent form and be able to understand and follow the procedures required by this protocol.

Exclusion criteria

• Diagnosed of acute promyelocytic leukemia (AML-M3)
• Patients with central nervous system (CNS) invasion.
• Cardiac function < grade 2.
• Known human immunodeficiency virus (HIV) infection.
• Other clinically significant uncontrolled conditions, including but not limited to: a. uncontrolled or active systemic infections (viruses, bacteria, or fungi); b. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; c. Secondary tumors requiring active treatment.
• Allergy to experimental drugs.
• Pregnant and lactating women.
• Patients who ineligible for the study according to the investigator's assessment.