Comparison of VA (Venetoclax, Azacitidine), VACl (VA, Cladribine), VACh (VA, Chidamide), and Alternating VACl/VACh in Newly Diagnosed Acute Myeloid Leukemia
Trial Parameters
Brief Summary
This prospective, multi-center, randomized, controlled Phase II study is to compare the therapeutic efficacy and side effect of VACl (Venetoclax,Azacitidine,Cladribine) alternating with VACh (Venetoclax,Azacitidine,Chidamide), VACl, VACh and VA in newly diagnosed adult acute myeloid leukemia (AML) patients ineligible for intensive therapy or declining. Cladribine is a purine analogue widely used in hematologic malignancies. The monocytic leukemia stem cell is selective sensitivity to Cladribine. Chidamide, a newly designed selective histone deacetylase inhibitor, could down regulate myeloid cell leukaemia 1 (MCL1) expression in Venetoclax resistant AML cells. Chidamide or Cladribine have synergistic anti-leukemia effects with VA through their unique mechanisms, which can eradicate leukemia stem cells and prevent the occurrence of drug resistance.
Eligibility Criteria
Inclusion Criteria: A subject will be eligible for study participation if he/she meets the following criteria within 21 days prior to randomization. 1. Subject must have confirmation of previously untreated AML by World Health Organization (WHO) criteria, and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities. Prior therapy with hydroxyurea or a total dose of cytarabine no more than 0.5g (for emergency use for stabilization) is allowed. 2. Subject must be≥18 years of age with at least one of the following conditions: A)≥60 years of age; B) Patients aged \< 60 years who are unsuitable for standard induction therapy（Any other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy); C) The patient refused the conventional intensive chemotherapy. 3. Adequate organ function as defined below: A)liver function (bilirubin≤2mg/dL, aspartate transaminase (AST) and/or alanine transaminase (