SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is a two-stage, Phase II clinical trial for patients with relapsed or refractory Hodgkin Lymphoma. The purpose of stage I is to evaluate whether treatment with the study drug decitabine in combination with SHR-1210 is safe and more effective than treatment with SHR-1210 alone; and reverse the resistance of anti-PD-1 antibody in patients with HL who had previously treated with anti-PD-1 monotherapy. If it is deemed that the combination therapy is more efficacious than SHR-1210 monotherapy (The CR rate of the combination group is at least 30% higher compared to monotherapy group with a minimal follow-up of 6 months in predicting 60 subjects naïve to anti-PD-1 antibody who are randomly assigned (2:1) to the above two groups), the stage II study will be revised to a multicohort, decitabine-plus-SHR1210 single-arm clinical trial. The primary objective of stage II study is to evaluate the long-term response duration with decitabine-plus-SHR-1210 in relapsed or refractory Hodgkin Lymphoma.

Official Title
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Anti-PD-1 Antibody SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma:an Open-label Phase II Trial

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: SHR-1210
* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 Subjects must have histological confirmation of relapsed or refractory Hodgkin lymphoma (HL). 2 12 to 75 years of age. 3 ECOG performance of less than 2. 4 Life expectancy of at least 3 months. 5 Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria. 6 Subjects must have received at least four prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.Subjects with Anti-PD-1 antibody are eligible which must be resistance. 7 Subjects must have adequate marrow, live, renal and heart functions. Exclusion Criteria: 1 Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications. 2 Serious uncontrolled medical disorders or active infections, pulmonary infection especially. 3 Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month . 4 Prior organ allograft. 5 Women who are pregnant or breastfeeding. 6 Women with a positive pregnancy test on enrollment or prior to investigational product administration. 7 Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1210-plus-Decitabine<br>Decitabine 10 mg/day, days 1-5; SHR-1210 200 mg, day 8, every 3 weeks. | Drug: SHR-1210<br>* SHR-1210 is a humanized anti-PD-1 monoclonal antibody.<br>Drug: Decitabine<br>* Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.<br>|
| Experimental: SHR-1210<br>SHR-1210 200 mg, day 1, every 3 weeks. | Drug: SHR-1210<br>* SHR-1210 is a humanized anti-PD-1 monoclonal antibody.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stage I: Number of Subjects with treatment-related adverse events (AEs) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. | 2 years | 
| stage I: CRR assess by investigators per the 2014 Lugano classification | rate of subjects achieved complete response in all evaluable subjects | 3 years | 
| stage II: duration of CR | Time measured from the day of first documented CR to the date of first documented progression, or death from any cause. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stage II: duration of response | Time measured from the day of first documented PR or CR to the date of first documented progression, or death from any cause. | 5 years | 
| stage II: Progression free survival | Time measured from the day of treatment to the date of first documented progression, or death from any cause. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/Refractory; Hodgkin Lymphoma；Decitabine; SHR-1210