Prospective, Open-label, Single Arm Trial to Evaluate Efficacy and Safety of Tislelizumab with Azacitidine in the Treatment of Refractory/relapsed Acute Myeloid Leukemia
Overview
- Phase
- Phase 1
- Intervention
- Aza, tislelizumab
- Conditions
- Refractory AML
- Sponsor
- Institute of Hematology & Blood Diseases Hospital, China
- Locations
- 1
- Primary Endpoint
- composite complete remission rate
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
Acute myeloid leukemia(AML) is a clonal hematological malignancy. 50%-90% adult AML patients can achieve complete remission(CR) after standard induction chemotherapy,but 10%-25% patients cannot achieve CR, which is called 'primary refractory disease'.Most of patients who achieved CR will relapse during the next 3 years, and the prognosis is poor.So refractory and relapse diseases are still the hotspot of clinical research.Immunologic escape is one of the mechanisms for tumor cells to survive from chemotherapy. Studies have shown that PD1 and PDL1 levels are upregulated in AML patients, the same phenomenon was observed after the treatment of demethylating agents such as azacytidine. Combination of PD1 blockades with azacytidine may improve the efficacy of the treatment.
Detailed Description
In this phase 1/2 study, 20 patients will be enrolled and treated with azacytidine and tislelizumab regimen. The primary endpoint is composite complete remission rate.Toxicities of treatment need to be observed. And relationship between PDL1 expression on AML cells and efficacy will be studied. Treatments include azacytidine 75mg/m2/d, subcutaneous injection,day1-7, every 28 days for three cycles tislelizumab 200mg,day 8,every three weeks, for 4 doses.
Investigators
Eligibility Criteria
Inclusion Criteria
- •diagnosis of AML according to FAB or WHO criteria
- •refractory or morphological relapsed AML
- •age over 18 years old
- •ECOG PS 0-2
- •written informed consent
Exclusion Criteria
- •acute promyelocyte leukemia
- •solitary extramedullary relapsed disease
- •other hematological diseases
- •antecedent stem cell transplantation
- •AML with BCR_ABL positive
- •acute panmyelosis with myelofibrosis or sarcoma
- •with other active organ malignancy(needing treatment)
- •active heart diseases
- •unfit for enrollment after investigator's evaluation
Arms & Interventions
treatment arm
azacytidine 75mg/m2/d, IH,day1-7, every 28 days for three cycles tislelizumab 200mg,day 8,every three weeks, for 4 doses
Intervention: Aza, tislelizumab
Outcomes
Primary Outcomes
composite complete remission rate
Time Frame: up to 2 years
including complete remission plus complete remission with incomplete blood cell count recovery
Secondary Outcomes
- overall survival(up to 4 years)
- disease free survival(up to 4 years)