Sintilimab in Combination With Chidamide in Refractory and Relapsed ENKTCL
Condition: Safety and Efficacy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    


Intervention name(s): Sintilimab; Chidamide
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Tyvyt®; Epidaza
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sintilimab; Chidamide; refractory and relapsed; Extranodal natural killer cell/T-cell lymphoma