Anti-PD-1 Antibody Combined With Pegaspargase in the Treatment of Advanced Stage NK/T-cell Lymphoma

Study Overview
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Brief Summary
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This open-label, single arm study will evaluate the efficacy and safety of anti-PD-1 antibody in combination with pegaspargase in treatment of newly diagnosed advanced stage NK/T-cell lymphoma.

Detailed Description
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Extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type, is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for 5% 10%. The frequency of ENKTL among NHL patients is significantly higher in Asia than in Western countries, with poor prognosis. L-asparaginase-based chemotherapy has improved the survival for these patients with advanced stage. However, there is no standard of care for those patients with advanced stage. Anti-PD-1 antibody has been proven its efficacy in relapsed or refractory NK/T cell lymphoma. This open-label, single arm study will evaluate the efficacy and safety of PD-1 antibody in combination with pegaspargase in treatment of newly diagnosed advanced stage NK/T-cell lymphoma.

Official Title
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The Efficacy and Safety of Anti-PD-1 Antibody in Combination With Pegaspargase in the Treatment of Newly Diagnosed, Stage III to IV Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

Conditions
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Nasal Type Extranodal NK/T-Cell Lymphoma

Intervention / Treatment
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* Drug: Pegaspargase
* Drug: Anti-PD-1 monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed NK/T cell lymphoma based on 2016 WHO classification Treatment naive Age > 18 years Advanced stage Must has measurable lesion in CT or PET-CT prior to treatment ECOG 0,1,2 Informed consented Exclusion Criteria: Aggressive NK/T-cell leukemia Has accepted PD-1,PD-L1 or PD-L2 antibody before Has accepted autologous Stem cell transplantation before History of malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix 3 years prior to study treatment Uncontrollable cardio-cerebral vascular, coagulative, autoimmune, serious infectious disease Primary CNS lymphoma Lab at enrollment (Unless caused by lymphoma): Neutrophile<1.5*10^9/L ;Platelet<50*10^9/L; ALT or AST >3*ULN; Creatinine>2*ULN Other uncontrollable medical condition that may that may interfere the participation of the study Not able to comply to the protocol for mental or other unknown reasons Pregnant or lactation HIV infection HBV-DNA or HCV-RNA positive Diagnosed immunodeficiency or received systemic corticoid therapy 2 weeks prior to first dose. Received attenuated live vaccine 4 weeks prior to first dose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-PD-1 antibody plus pegaspargase<br>Participants will receive induction treatment for six cycles of Anti-PD-1 antibody plus pegaspargase (21-day cycle) and Anti-PD-1 antibody monotherapy maintenance treatment for about 2 years (21-cycle) | Drug: Pegaspargase<br>* Pegaspargase 3750IU administered by intramuscular injection on Day 1 of each 21-day cycle for 6 cycles in induction treatment<br>Drug: Anti-PD-1 monoclonal antibody<br>* Anti-PD-1 antibody 200mg administered intravenously (IV) on Day 2 of each 21-day cycle for 6 cycles in induction treatment Anti-PD-1 antibody 200mg administered intravenously (IV) on Day 1 of each 21-day cycle for up to 28 cycles in maintenance treatment<br>* Other names: Tyvyt;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. | At the end of Cycle 6 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. | At the end of Cycle 6 (each cycle is 21 days) | 
| Progression free survival | Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy, or death from any cause, whichever occurred first. | Baseline up to data cut-off (up to approximately 4 years) | 
| Overall survival | Overall survival in the overall study population was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. | Baseline up to data cut-off (up to approximately 4 years) | 
| Duration of response | Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT. | Baseline up to data cut-off (up to approximately 4 years) | 
| EBV-DNA load change | EBV-DNA load at each cycle for comparison | End of induction treatment (approximately 1 year) | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Baseline up to data cut-off (up to approximately 4 years) | 
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores | The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants. | Baseline (pre-dose [Hour 0] on Cycle1 Day1), Cycle3 Day 1, end of treatment (up to Month 6), every 3 months 1st year, every 6 months 2nd year, and 12 months thereafter up to data cut-off, up to approximately 4 years (cycle length = 21 days) | 
| Treatment related mortality | Percentage of death related with treatment on the basis of investigator assessments | Baseline up to data cut-off (up to approximately 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-PD-1 antibody, Nasal Type Extranodal NK/T-Cell Lymphoma, Complete response rate, Safety