Phase II Study of Sintilimab Plus R-CHOP as the First-line Treatment for DLBCL Patients With TP53 Mutation and PD-L1 Positive.
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 主要终点
- complete remission rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed as diffuse large B-cell Lymphoma with positive CD20 results;
- •Age between 18 to 70 years old;
- •World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2;
- •No history of malignant tumors, having no tumor other than DLBCL at the time of enrollment;
- •Life expectancy no less than 6 months;
- •The patient or his/her attorney would be able to provide written consent for necessary examinations or procedures;
- •Ann Arbor stage I~ IV
- •previously untreated advanced DLBCL.
- •At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
- •Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of DLBCL.
- •Agree to remain abstinent or use contraceptive measures.
排除标准
- •History of autologous stem cell transplantation,radiotherapy or chemotherapy.
- •History of other malignant tumors, except skin basal cell carcinoma and in situ cervical cancer;
- •With uncontrolled cardiovascular/ cerebrovascular disease, coagulation disorders, connective tissue disease, severe infectious diseases;
- •Lymphoma originated in the central nervous system;
- •Left ventricular ejection fraction ≦50％;
- •Abnormal lab results in enrollment:Neutrophil count: <1.5*10^9/L；Platelet count <75*10^9/L；AST or ALT >2 times the upper limit of normal level，AKP and total bilirubin >1.5 times the upper limit of normal level;serum creatinine >1.5 times the upper limit of normal level;
- •Other uncontrolled medical conditions which the investigators think might influence the results of the trial;
- •Patients with mental illnesses or other diseases that might not comply with the trial plan;
- •Women during pregnancy or lactation;
- •HIV positive patients;
- •HbsAg (+) patients with HBV DNA(+), can be enrolled only when his/her HBV DNA turns negative; patients with HBsAg(-) HBcAb(+) can be enrolled only when his/her HBV DNA turns negative;
研究组 & 干预措施
Sintilimab-R-CHOP
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.
干预措施: Sintilimab-R-CHOP (Drug)
结局指标
主要结局
complete remission rate
时间窗: every 3 months until 30 months after the last patient's enrollment.
complete remission rate after treated by Sintilimab+ R-CHOP regimen.
次要结局
- overall survival(30 months after the last patient's enrollment)
- adverse events(from the date of first cycle of treatment to 30 months after last patient's enrollment)
研究者
Shi Yuankai
vice president
Chinese Academy of Medical Sciences