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.
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.
ECOG performance status of ≤ 2.
A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
Subject has acute promyelocytic leukemia, subject has history of myeloproliferative neoplasm [MPN] including myelofibrosis, essential thrombocythemia, polycythemia vera, CML with or without BCR-ABL1 translocation, BCR/ABL positive AML.
Patient has known active central nervous syster (CNS) involvement with AML.
Subject has a white blood cell count> 25×10^9/L. (Hydroxyurea is permitted to meet this criterion.)
Prior therapy with venetoclax, Cladribine, hypomethylating agents (HMAs), Chidamide or Chimeric Antigen Receptor T cell therapy, experimental therapies for MDS or AML.
The First Affiliated Hospital of Soochow University
Lead sponsor
Jining Medical University
Collaborator
Qilu Hospital of Shandong University
Collaborator
The Affiliated Hospital of Qingdao University
Collaborator
The First Affiliated Hospital of Anhui Medical University
Collaborator
Tongji Hospital
Collaborator
The First Affiliated Hospital of Bengbu Medical University
Collaborator