This study is to investigate the therapeutic efficacy and side effect of venetoclax, azacytidine combined with chidamide for newly diagnosed acute monocytic leukemia patients that are ineligible for intensive chemotherapy
Acute myeloid leukemia (AML) is one of the most aggressive blood cancers, with a very low survival rate and few options for patients who are unable to undergo intensive chemotherapy. Venetoclax in combination with hypomethylation agents or cytarabine has been approved by the Food and Drug Administration (FDA) for the treatment of patients with newly diagnosed AML unfit for intensive chemotherapy. However, resistance to venetoclax can be acquired through the upregulation of anti-apoptotic proteins in the BCL2 family, such as myeloid cell leukaemia 1 (MCL1). MCL1 plays a critical role in cell apoptosis regulation and high expression of MCL1 is observed in acute monocytic leukemia (AML-M5) . Chidamide, a newly designed selective histone deacetylase inhibitor, resulted in a decrease in the protein level of MCL1. This study is to investigate the therapeutic efficacy and side effect of venetoclax, azacytidine combined with chidamide for newly diagnosed AML-M5 patients that are ineligible for intensive chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Chidamide 10mg orally daily for 7 days (d1-d7)
azacytidine 75mg/m2 daily for 7 days (d1-d7)
Venetoclax orally once daily (100 mg d1, 200 mg d2, 400 mg d3-28)
The First Affliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGComposite Complete Remission Rate
The composite complete remission rate(complete remission plus complete remission with incomplete blood cell count recovery)
Time frame: At the end of Cycle 1 or 2 (each cycle is 28 days)
Overall response rate (ORR)
The overall response (completed remission without minimal residual disease, completed remission with incomplete blood count recovery, morphologic leukemia-free state and partial remission)
Time frame: At the end of Cycle 1 or 2 (each cycle is 28 days)
Duration of Response (DOR)
It is measured the time from initial response to subsequent disease progression or relapse
Time frame: 1 year
Overall Survival (OS)
It is measured from the time of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive
Time frame: 1 year
Progression-Free Survival (PFS)
It is measured from the time from randomization to progression or death
Time frame: 1 year
Adverse reactions in hematology
Record of adverse events in hematological system during and after VEN+AZA+Chidamide regimen induction (agranulocytosis days, PLT/RBC transfusion units)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Nonhematological adverse reactions
Record of adverse events in other organs or systmes during and after VEN+AZA+Chidamide regimen induction (infection and organ injury)
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Time frame: At the end of Cycle 1 (each cycle is 28 days)