This phase II trial studies how well tislelizumab combined with DNA hypomethylation agent +/- CAG regimen (cytarabine, idarubicin / Aclarithromycin, rhG-CSF/ PEG-rhG-CSF) work in treating patients with high-risk acute myeloid leukemia (AML) or AML patients older than 60 years of age who are unfit for standard-dose chemotherapy. The expressions of PD-1 and PD-L1 are increased in AML cells. However, blocking the immune checkpoint alone has limited efficacy as a single agent in highly proliferative leukemia cells. During the recovery period after cytotoxic chemotherapy, the activation of PD-1/PD-L1 pathway may be increased and DNA hypomethylation agents can also up-regulate PD-1, PD-L1 and PD-L2 in AML patients. The up-regulation and activation of above immune checkpoint molecules are related to chemotherapy resistance. Therefore, adding chemotherapy and epigenetic regulation agents to Immune checkpoint blockade therapy may work better through overcoming drug resistance in AML treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Tislelizumab combined with DNA demethylation agent +/- CAG regimen
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGObjective response rate (ORR)
The percentage of subjects with complete remission (CR) and incomplete hematological recovery (CRi) within 2 medication cycles.
Time frame: Up to 3 months post-treatment
The percentage of subjects with CR and CRi with negative minimal residual disease (MRD) within 2 cycles.
Time frame: Up to 3 months post-treatment
Duration of Remission (DOR)
The time from first obtaining CR or CRi to relapse or death from AML.
Time frame: Up to 1 year post-treatment
Progression-free survival time (PFS)
the time from the day of treatment to relapse, progression or death (whichever occurs first is preferred).
Time frame: Up to 1 year post-treatment
Overall survival (OS)
The time from the day of treatment to death.
Time frame: Up to 1 year post-treatment
28-day response rate
The percentage of subjects with CR and CRi (calculated based on the best response) at the 28th day after treatment.
Time frame: Up to 35 days post-treatment
Incidence of adverse events
The incidence of adverse events will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 35 days post-treatment
PD-L1 expression in acute myeloid leukemia bone marrow cells
The expression levels of PD-L1 in acute myeloid leukemia bone marrow cells will be assessed at the 28th day after each medication cycle.
Time frame: Up to 1 year post-treatment
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