Sintilimab in Combination With R-CHOP in Patients With Treatment-naive EBV-positive DLBCL, NOS

Study Overview
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Brief Summary
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The prognosis of EBV+ DLBCL is dismal. Previous study showed that high level of PD-L1 expression in EBV+ DLBCL. The investigators therefore design this phase II study to investigate the safety and efficacy of sintilimab (an anti-PD-1 antibody) in combination with R-CHOP in patients with treatment-naive EBV+ DLBCL.

Official Title
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A Phase II, Prospective, Multi-center Study of Sintilimab in Combination With R-CHOP in Patients With Treatment-naive EBV-positive DLBCL, NOS

Conditions
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EBV-Positive DLBCL, Nos

Intervention / Treatment
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* Drug: Sintilimab
* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Histologically confirmed EBV-positive diffuse large B cell lymphoma, NOS, according to WHO 2016 criteria. 2. Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements. 3. Undergo whole-body PET/CT scan 28 days before enrolment and have a measurable or evaluable disease (nodal lesion: diameter ≥ 1.5cm; extranodal lesion≥1.0cm）according to Lugano 2014 criteria； 4. ECOG PS 0- 2; 5. Adequate organ function, defined as: Blood routine test: neutrophil count ≥ 1.0×10⁹/L, platelet count ≥ 50×10⁹/L, hemoglobulin ≥8.0g/dL, without G-CSF usage or blood infusion within 7 days before examination. Hepatic function: total bilirubin less than 1.5-fold of upper normal level; ALT and AST less than 2-fold of upper normal level. Renal function: Serum creatine less than 1.5-fold of upper normal level or Ccr ≥ 50 mL/min. Cardiac function: New York Heart Association class II or below (EF≥ 50% according to TDE) Coagulative function: INR less than 1.5-fold of upper normal level, APTT less than 10s above upper normal level and PT less than 3s above upper normal level; Thyroid function: normal baseline TSH level, or abnormal baseline TSH but normal T3/T4 level without symptoms; 6. Expected survival ≥ 3 months; 7. Age 18 70 years; 8. Female subjects in childbearing age, their serum or urine pregnancy test must be negative. All patients must agree to take effective contraceptive measures during treatment and 90 days after treatment. Exclusion Criteria: CNS or meningeal involvement; Patients with secondary tumour, excluding cured (5 years without relapse) in situ Non-melanoma skin cancer. superficial bladder cancer, in situ cervical cancer, Gastrointestinal intramucous carcinoma and breast cancer; Known sensitivity or allergy to investigational product; Previous exposure to anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2 antibody, anti CTLA-4 antibody, CAR-T therapy or any T cell co-stimulating antibody or checkpoint inhibitor; Previous allogeneic organ transplantation or allogeneic stem cell transplantation; Intention to use any other anti-tumour therapy during treatment; Use of systemic anti-tumour treatment within 3 months before first dose of study regimen; Active and severe infectious diseases requiring systemic treatment; Active (known or suspected) autoimmune disease or history of autoimmune disease within 2 years before treatment (excluding patients with leukoderma, psoriasis, lipsotrichia or Grave's disease who do not require systemic treatment within 2 years, patients with hypothyrea only requiring thyroxine as treatment, and patients with type I diabetes but only requiring insulin treatment) Usage of immune inhibitory drugs 4 weeks before the first dose of study regimen, excluding local usage of glucocorticoid and systemic usage of less than 10mg/d Prednisone or equivalent glucocorticoid. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons; Previous history of Idiopathic pulmonary fibrosis or Idiopathic pneumonia; Active tuberculosis; Presence of ≥ Grade 3 immune therapy related toxicity; History of mental disorder including epilepsia and dementia; Any anti-infectious vital vaccine usage 4 weeks before the first dose or during treatment; Any potential drug abuse, medical, psychological or social conditions which may disturb this investigation and assessment; Women who are pregnant or lactating. Usage of other experimental drugs within 1 month before treatment; In any conditions which investigator considered ineligible for this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Sintilimab + R-CHOP<br> | Drug: Sintilimab<br>* Sintilimab 200mg d0<br>Drug: Rituximab<br>* Rituximab 375 mg/m2 d0<br>Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m2 d1<br>Drug: Doxorubicin<br>* Doxorubicin 50 mg/m2 d1<br>Drug: Vincristine<br>* Vincristine 1.4mg/m2 (maximum 2mg) d1<br>Drug: Prednisolone<br>* Prednisolone 60mg/m2 d1-5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progressive free survival | from date of inclusion to date of progression, relapse, or death from any cause | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | overall response rate after treated by Sintilimab and R-CHOP | 6 months | 
| Overall survival | from the date of inclusion to date of death, irrespective of cause | 2 years | 
| Incidence of treatment related adverse events as assessed by NCI-CTCAE 5.0 |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sintilimab, R-CHOP, EBV-Positive DLBCL, nos, treatment-naive