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

A Multicenter, Prospective, Randomized Controlled Study Comparing the Efficacy and Safety of CLAG(Cladribine, Cytarabine and G-CSF) Combined With Venetoclax and CLAG in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) 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:

1. Diagnosed of AML according to the World Health Organization (WHO) classification.
2. All patients should aged 18 to 65 years.
3. Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
4. 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.
5. 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.
6. The score of Eastern Cooperative Oncology Group (ECOG) is 0-2.
7. Renal function: creatinine clearance rate ≥ 30ml/min.
8. Liver function: ALT<5 times normal value, bilirubin<3 times normal value.
9. Predicted survival ≥ 3 months.
10. Able to accept oral Venetoclax.
11. Sign an informed consent form and be able to understand and follow the procedures required by this protocol.

Exclusion Criteria:

1. Diagnosed of acute promyelocytic leukemia (AML-M3)
2. Patients with central nervous system (CNS) invasion.
3. Cardiac function < grade 2.
4. Known human immunodeficiency virus (HIV) infection.
5. 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.
6. Allergy to experimental drugs.
7. Pregnant and lactating women.
8. Patients who ineligible for the study according to the investigator's assessment.