Clinical trial NCT04231370: Lenalidomide and Sintilimab for Relapsed/Refractory NK/T-cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: NK/T Cell Lymphoma Nos
Keywords: pegaspargase
sintilimab
PD-1
lenalidomide
relapsed/refractory
Lead sponsor: Beijing Tongren Hospital
Sponsor class: OTHER
First posted: 2020-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: treatment with lenalidomide in combination with sintilimab for relapsed/refractory ENKTCL patients
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of complete response
timeFrame: 24 weeks ±7 days
Secondary outcomes:
measure: Rate of overall response
timeFrame: 24 weeks ±7 days
measure: 1-year progression free survival rate
timeFrame: up to 1year after enrollment
measure: 1-year overall survival rate
timeFrame: up to 1year after enrollment
measure: safety profiles
timeFrame: up to 1year after enrollment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tongren Hospital
Study officials:
affiliation: Beijing Tongren Hospital
name: Jing-wen Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: