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The purpose of this study is to evaluate the efficacy and safety of Sintilimab and R-CHOP regimen as the first-line treatment for DLBCL patients with TP53 mutation and PD-L1 positive.
This Phase II, open-label, single-center, non-randomized study will evaluate the safety and efficacy of induction treatment consisting of Sintilimab in combination with Rituximab plus chemotherapy (R-CHOP) as the first-line treatment in participants with DLBCL, followed by consolidation treatment with Sintilimab alone in patients who achieve CR at the end of induction.For safety reasons, the initial enrollment of the first 6 patients in the study will be slow and conduct intensive monitoring for safety. If the dose-limited toxicity event was observed in more than 2 of the first 6 patients and was assessed caused by cumulative exposure to the study drug combination therapy, the trial will be stopped.This study also aim to evaluate the correlation of clinical efficacy to the expression of PD-L1,PD-1,CD3,CD4,CD8,CD56,CD58,β2-MG,HLA-DR/DP/DQ and so on by immunohistochemical techniques.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sintilimab-R-CHOP | Experimental | Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and Sintilimab, rituximab, and CHOP during Cycles 2-6 (21-day cycle) ,Sintilimab and rituximab during Cycles 6-8 (21-day cycle) , followed by Sintilimab from Cycles 9-14 (8-week cycle) during consolidation treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sintilimab-R-CHOP | Drug | Drug:Sintilimab: Sintilimab:200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 200 mg IV on Day 1 of Cycles 9-14. Drug: Rituximab Rituximab:Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m^2 IV on Day 1 of Cycle 1-8, during induction treatment. Drug: Cyclophosphamide Cyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 2 of Cycle 1-6, during induction treatment. Drug: Doxorubicin Hydrochloride Liposome Injection Doxorubicin Hydrochloride Liposome Injection will be administered at a dose of 35 mg/m^2 IV on Day 2-3 of Cycle 1-6, during induction treatment. Drug: Vincristine Vincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 2 of Cycle 1-6, during induction treatment. Drug: Prednisone Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6, during induction treatment. Prednisolone may be given if prednisone is unavailable. |
| Measure | Description | Time Frame |
|---|---|---|
| complete remission rate | complete remission rate after treated by Sintilimab+ R-CHOP regimen. | every 3 months until 30 months after the last patient's enrollment. |
| Measure | Description | Time Frame |
|---|---|---|
| overall survival | from the date of inclusion to date of death, irrespective of cause | 30 months after the last patient's enrollment |
| adverse events | any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.For safety reasons, the initial enrollment of the first 6 patients in the study will be slow and conduct intensive monitoring for safety. the monitoring time window for each patient is 21 days after the first treatment. If the dose-limited toxicity event was observed in more than 2 of the first 6 patients and was assessed by the research team as caused by cumulative exposure to the study drug combination therapy, the trial will be stopped. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuankai Shi, M.D | Contact | 86 010-87788293 | syuankaipumc@126.com | |
| Yan Qin, M.D | Contact | 86 010-87788293 | 13601282738@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Yuankai Shi, M.D | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
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| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
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| from the date of first cycle of treatment to 30 months after last patient's enrollment |
| D009369 |
| Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |