Combined Chemotherapy and PD-1 Antibody(SHR-1210) With or Without Low-dose Decitabine Priming for Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL):Two Stage, Phase I/II Trail
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Number of Subjects with treatment-related adverse events (AEs)
研究概览
简要总结
This is a two stage, Phase I/II clinical trial for patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL). In the first stage, the participants will receive GVD (Gemcitabine, Vinorelbine and Doxorubicine) chemotherapy and PD-1 antibody (SHR-1210) treatment. The safety and efficacy of combined regimen will be evaluated. If deemed safe and efficacious, the investigators will proceed to the second stage of the study. In the second stage, the participants will receive GVD chemotherapy and SHR-1210 treatment with low-dose Decitabine priming. The safety and feasibility of combined regimens will be evaluated in phase I study. The feasibility will be accessed.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients had histologically proven PMBCL, and Radiographically measureable disease.
- •Eastern Cooperative Oncology Group performance status 0-2
- •Disease recurring within 6 months after first-line chemotherapy or disease progression while receiving or persistent disease after first-line chemotherapy
- •Bulky disease was defined as the presence of a mediastinal mass > 4.5 cm in axial diameter or extranodal lesion > 3 cm.
- •Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day
- •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.
- •Adequate organ function.
- •Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
- •Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.
排除标准
- •Known clinically active central nervous system involvement.
- •Any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- •Serious uncontrolled medical disorders or active infections, pulmonary infection especially
- •Prior organ allograft.
- •Receiving any other form of immunosuppressive medication, except steroid.
- •Allogeneic hematopoietic stem cell transplantation within the last 5 years. 6） Known human immunodeficiency virus (HIV). 7） Has received a live vaccine within 30 days prior to first dose of study drug.
- •8） Women who are pregnant or breastfeeding.
研究组 & 干预措施
GVD and SHR-1210 with or without Decitabine
This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed.
干预措施: Decitabine (Drug)
GVD and SHR-1210 with or without Decitabine
This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed.
干预措施: GVD chemotherapy (Drug)
GVD and SHR-1210 with or without Decitabine
This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed.
干预措施: SHR-1210 (Drug)
结局指标
主要结局
Number of Subjects with treatment-related adverse events (AEs)
时间窗: Up to 120 days after last administration of SHR-1210
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Objective response rate (ORR)
时间窗: Enrolled patients will be followed until death, withdrawal from study, or until 2 years.
The antitumor efficacy of the combination treatments as measured by ORR was determined using the International Working Group 2007 criteria for malignant lymphoma (J Clin Oncol. 2007 Feb 10;25(5):579-586). Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment. ORR is defined as the sum of CR and PR.
次要结局
- Median progression-free survival (PFS) time(Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.)
- Complete response (CR) rate(Up to 2 years after completion of study treatment)
- Median overall survival (OS) time(Patients will be followed until death, withdrawal from study, or until 2 years.)
研究者
Han weidong
Principal Investigator
Chinese PLA General Hospital