NCT03820596

Sintilimab in Combination With Chidamide in Refractory and Relapsed ENKTCL

Safety and Efficacy of Sintilimab(S) in Combination With Histone Deacetylase Inhibitor (Chidamide, C) in Refractory and Relapsed Extranodal Natural Killer Cell/T-cell Lymphoma(EN): A Single-arm, Multicenter Phase I b/II Study(SCENT)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Huiqiang Huang · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Safety and Efficacy

Interventions

Type	Name	Description
DRUG	Sintilimab	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.
DRUG	Chidamide	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.

Timeline

• Start date: 2019-03-29
• Primary completion: 2020-05-20
• Completion: 2021-11-30
• First posted: 2019-01-29
• Last updated: 2022-04-14

Locations

4 sites across 1 country: China