Lenalidomide and Sintilimab for Relapsed/Refractory NK/T-cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of Sintilimab in combination with lenalidomide in the treatment of Relapsed/Refractory NK/T-cell lymphoma patients who failed pegaspargase-based regimens.

Detailed Description
-----------------
Pegaspargase is the backbone of treatment for NK/T-cell lymphoma (ENKTCL), and patients with ENKTCL who failed pegaspargase-based regimens have extremely poor survival outcomes. Previous study has confirmed the efficacy of anti-PD-1 antibodies (including pembrolizumab or sintilimab). Constitutive activation of NF-kB pathway has been demonstrated to be involved in the development of ENKTCL and plays critical role in therapy resistance. Lenalidomide, an immuno-modulatory drug, has been found to inhibit NF-kB pathway, and synergize with anti-PD-1 antibody in the treatment of multiple myeloma. Thus, we hypothesize that the combination of lenalidomide and sintilimab will further deepen the remission status and benefit patients who failed pegaspargase-based regimens.

Official Title
-----------------
Combination of Lenalidomide and Sintilimab for Patients With Relapsed/Refractory NK/T-cell Lymphoma Who Failed Pegaspargase-based Regimens: a Single Arm, Open, Phase II Study

Conditions
-----------------
NK/T Cell Lymphoma Nos

Intervention / Treatment
-----------------
* Drug: Sintilimab
* Drug: Lenalidomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histopathology and immunohistochemistry confirmed diagnosis of NK/T-cell lymphoma according to WHO 2016 criteria. Previously treated with pegaspargase-based regimens (refractory or relapsed after initial remission). PET/CT or CT/MRI with at least one objectively evaluable lesion. General status ECOG score 0-3 points. The laboratory test within 1 week before enrollment meets the following conditions: Blood routine: Hb>80g/L, PLT>50×10（9）/L. Liver function: ALT, AST, TBIL ≤ 2 times the upper limit of normal. Renal function: Cr is normal. Coagulation : plasma fibrinogen ≥ 1.0g / L. Cardiac function: LVEF≥50%, ECG does not suggest any acute myocardial infarction, arrhythmia or atrioventricular conduction above I Blocking. Sign the informed consent form. Voluntary compliance with research protocols, follow-up plans, laboratory and auxiliary examinations. Exclusion Criteria: Patients with a history of pancreatitis. Active infection requires ICU treatment. Concomitant HIV infection or active infection with HBV, HCV. Patients who are infected with HBV but not active hepatitis at the same time are not excluded. Serious complications such as fulminant DIC. Significant organ dysfunction: such as respiratory failure, NYHA classification ≥ 2 chronic congestive heart failure, decompensation Hepatic or renal insufficiency, high blood pressure and diabetes that cannot be controlled despite active treatment, and cerebral vascular thrombosis or hemorrhagic time within the past 6 months. Pregnant and lactating women. Had a history of autoimmune diseases, and disease was active in the last 6 months, and was still taking oral immunosuppression in the past three months. Those who were known to be allergic to drugs in the study regimen. Patients with other tumors who require surgery or chemotherapy within 6 months. Other experimental drugs are being used.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: treatment with lenalidomide in combination with sintilimab for relapsed/refractory ENKTCL patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br>Sintilimab, 200mg, iv day1 Lenalidomide, 25mg/d, oral, day 1-14 repeated every 3 weeks | Drug: Sintilimab<br>* Sintilimab, 200mg, iv day1<br>* Other names: anti-PD-1-antibody;Drug: Lenalidomide<br>* 25mg/d oral d1-14<br>* Other names: IMids;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete response | evaluated by PET-CT and MRI, according to Lugano 2014 criteria | 24 weeks ±7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall response | evaluated by PET-CT and MRI, according to Lugano 2014 criteria | 24 weeks ±7 days | 
| 1-year progression free survival rate | time from date of enrollment to date of disease progression, death of any reason, whichever comes first | up to 1year after enrollment | 
| 1-year overall survival rate | time from date of enrollment to date of death of any reason | up to 1year after enrollment | 
| safety profiles | according to CTCAE 4.0 | up to 1year after enrollment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pegaspargase, sintilimab, PD-1, lenalidomide, relapsed/refractory