Camrelizumab Combined With AVD in the First-line Treatment for Patients With Advanced Classical Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This is a prospective phase II clinical trial to observe the efficacy and safety of Camrelizumab combined with AVD in the first-line treatment for patients with advanced classical Hodgkin's lymphoma.

Detailed Description
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Hodgkin's lymphoma (HL) is a kind of malignant tumor of the lymph system, approximately 95% of which are classical hodgkin's lymphoma (cHL). Currently, ABVD and BEACOPP are commonly used in the first-line treatment for cHL. There are about one third of patients, whose pre-treatment assessment are mainly advanced cHL, suffering relapse and drug resistance. PD-1/PD-L1 signaling pathway plays an important role in the development and progression of cHL. Nivolumab and Pembrolizumab have been used in the therapy in relapsed and refractory patients with cHL. Camrelizumab, a humanized anti-PD-1 IgG4 monoclonal antibody, is independently developed in China. The goal of our trial is to assess the efficacy and safety of Camrelizumab combined with AVD (Epirubicin, Vincristine and Dacarbazine) in the first-line treatment for patients with advanced classical Hodgkin's lymphoma.

Official Title
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Phase II Clinical Trial of Camrelizumab Combined With AVD (Epirubicin, Vincristine and Dacarbazine) in the First-line Treatment for Patients With Advanced Classical Hodgkin's Lymphoma

Conditions
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Classical Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Camrelizumab
* Drug: Epirubicin
* Drug: Vincristine
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 to 75 years old (including 18 and 75) Diagnosed as advanced classical hodgkin's lymphoma based on histopathology Subjects must be untreated (Ann Arbor Stage III/IV or Ann Arbor II with B symptoms along with mediastinal big tumor or extranodal changes) No receiving chemotherapy before enrollment Having at least one measurable lesions World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1 Life expectancy no less than 3 months enough main organ function Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study Agreeing to sign the written informed consents Exclusion Criteria: Diagnosed as nodular lymphocyte predominant lymphoma or grey-zone lymphoma Diagnosed as central nervous system lymphoma usage of immunosuppressants before enrollment and the dose of immunosuppressant used >10mg / day oral prednisone for more than 2 weeks Previously treated with anti-PD-1/PD-L1/PD-L2/CTLA-4 Active autoimmune disease Vaccination with anti-tumor vaccine or other immune treatments less than 3 months Serious surgery and trauma less than two weeks Other malignant tumor history or active malignant tumor need be treated Systemic therapy for serious acute/chronic infection Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months Active tuberculosis Vaccination with live attenuated vaccine less than 4 weeks HIV-positive, AIDS patients and untreated active hepatitis Researchers determine unsuited to participate in this trial

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab Combined With AVD regimen<br>Camrelizumab 200mg, Intravenous administration on day 1 and day 15 combined with regimen：AVD (Epirubicin, Vincristine and Dacarbazine): repeated every 4 weeks, up to 6 cycles. | Drug: Camrelizumab<br>* 30mg, Intravenous administration on day 1 and day 15 of each 4-week cycle until disease progression or unacceptable toxicity develops, up to 6 cycles.<br>* Other names: SHR-1210;Drug: Epirubicin<br>* 35mg/m2, Intravenous administration on day 1 and day 15 of each 4-week cycle until disease progression or unacceptable toxicity develops, up to 6 cycles.<br>* Other names: Epirubicin hydrochloride;Drug: Vincristine<br>* 1.4mg/m2, Intravenous administration on day 1 and day 15 of each 4-week cycle until disease progression or unacceptable toxicity develops, up to 6 cycles.<br>* Other names: Oncovin;Drug: Dacarbazine<br>* 375mg/m2, Intravenous administration on day 1 and day 15 of each 4-week cycle until disease progression or unacceptable toxicity develops, up to 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the total proportion of patients with complete response (CR) and partial response (PR) | every 8 weeks from the day of the first cycle of treatment to 1 year after last patient's enrollment (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year progression-free survival | the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurrs first | from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment (each cycle is 28 days) | 
| overall survival | from date of first day of treatment to the date of death by any cause | from date of the first cycle of treatment to the date of death from any cause, assessed up to 5 years (each cycle is 28 days) | 
| incidence and relationship with study drugs of grade 3-4 adverse events and abnormal laboratory examinations | the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03) and abnormal laboratory examinations | from the date of the first cycle of treatment to 1 year after last patient's enrollment (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Classical Hodgkin Lymphoma, PD-1/PD-L1 Signaling Pathway, Camrelizumab