Extranodal natural killer/T cell lymphoma(ENKTCL) is a distinct lymphoid neoplasm with aggressive course and poor outcomes. Optimal treatment strategies for advanced ENKTCL have not been fully defined.Patients with disseminated or relapsed disease have a very poor outcome,and there is no standard management for relapsed or refractory disease.Combination chemotherapy remains the mainstay of treatment.In small retrospective studies have observed very good response and survival rates in patients treated with L-asparaginase.In several prospective study that examined relapsed/refractory patients treated with SMILE outside a trial setting,the efficacy sounds good. But treatment related mortality was 7%. The regimen has toxicity, with careful attention to adverse effects and skill acquired through experience. Chidamide, a oral subtype-selective histone deacetylase inhibitor monotherapy was effective on the patients with relapsed or refractory ENKTCL in our study. Objective response rate was 50.0% (6/12) with complete response(CR) rate 33.3 %( 4/12).All four CR patients were still in disease-free more than 6.9 months (6.9-10.5). ENKTCL are invariably infected by Epstein-Barr virus(EBV).EBV-infected lymphoma cells upregulate programmed death ligand 1 (PDL1), ligand of the inhibitory receptor programmed death 1(PD1) on T cells.Ligation of PDL1 on lymphoma cells with PD1 on effector T cells suppresses T-cell cytotoxicity. The PDL1/PD1 axis is therefore a potential mechanism for ENKTCL to avert effector T-cell targeting.PD1 blockadewith pembrolizumab was a potent strategy for ENKTCL failing L-asparaginase regimens in several reports.We carried out a single, open-label, multicenter clinical trial enrolled patients with relapsed or refractory ENKTCL to safety and efficacy of sintilimab in combination With chidamide.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
To evaluate the short-term objective efficacy of sintilimab combined with chidamide in the treatment of refractory and relapsed ENKTCL patients, and to determine the MTD, DLT/RP2D of chidamide. To evaluate the long-term efficacy and safety of sintilimab combined with chidmide in the treatment of refractory and relapsed ENKTCL patients. Exploring biomarkers that may have predictive effects.
To evaluate the short-term objective efficacy of sintilimab combined with chidamide in the treatment of refractory and relapsed ENKTCL patients, and to determine the MTD, DLT/RP2D of chidamide. To evaluate the long-term efficacy and safety of sintilimab combined with chidmide in the treatment of refractory and relapsed ENKTCL patients. Exploring biomarkers that may have predictive effects.
Department of hematology department, Nanfang hospital
Guangzhou, Guangdong, China
Guangdong General Hospital; Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
Sun Yat-sen University Cancer Center
Guangzhou, China
Phase 1 Study: Percentage of Participants Experiencing Adverse Events defined as Dose Limiting Toxicities (DLTs) of Chidamide.
Dose-limiting toxicity is defined as protocol-defined chidamide related events within the first 90 days
Time frame: Up to 90 days
Phase 1 Study: Maximum tolerable dose of chidamide among participants
Maximum tolerable dose is defined as protocol-defined the highest quantity chidamide among participants.
Time frame: Up to 90 days
Phase 1 Study: Maximum tolerable dose(MTD) and recommended Phase 2 dose (RP2D) of chidamide among participants
Maximum tolerable dose is defined as protocol-defined the highest quantity chidamide among participants.
Time frame: Up to 90 days
Phase 2 Safety Management Study
Incidence and Severity of Toxicities
Time frame: Up to12 months
Efficacy of sintilimab plus chidamide in refractory and relapsed ENKTCL
Objective response including CR and PR rate
Time frame: Up to 24 months
Progression-Free Survival (PFS)
PFS is defined as the time from the treatment date to the date of disease progression per the RECIL 2017 Response Criteria for Malignant Lymphoma or death regardless of cause.
Time frame: Up to12 months
Duration of Response (DOR)
Among participants who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression per the RECIL 2017 Response Criteria for Malignant Lymphoma or Among participants who experience an objective response.
Time frame: Up to12 months
Overall Survival (OS)
OS is defined as the time from treatment to the date of death.
Time frame: Up to 24 months
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