Pilot Study of Feasibility and Safety of Personalized Autologous CD8+ T Cell Therapy Plus Anti-PD1 Antibody in Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence of toxicity defined as grade 3 or 4 non-hematologic or grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 4.0
研究概览
简要总结
This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T cells in treating patients with gastrointestinal tumors that have spread to other places in the body. Tumor cells and blood are used to help create an adoptive T cell therapy, such as CD8+ T cell therapy, that is individually designed for a patient and may help doctors learn more about genetic changes in the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CD8+ T cell therapy and pembrolizumab may work better in treating patients with gastrointestinal tumors.
详细描述
PRIMARY OBJECTIVES:
I. Assess the safety of using a personalized adoptive T cell therapy in patients with advanced gastrointestinal malignancies.
SECONDARY OBJECTIVES:
I. Assess the persistence of an immune response after T cell infusion. II. Determine the clinical benefit of adoptive T cell therapy in advanced gastrointestinal cancers.
OUTLINE:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment (CD8 +T cell therapy, pembrolizumab)
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
干预措施: Adoptive Immunotherapy (Biological)
Treatment (CD8 +T cell therapy, pembrolizumab)
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
干预措施: Aldesleukin (Biological)
Treatment (CD8 +T cell therapy, pembrolizumab)
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
干预措施: Cyclophosphamide (Drug)
Treatment (CD8 +T cell therapy, pembrolizumab)
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (CD8 +T cell therapy, pembrolizumab)
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Incidence of toxicity defined as grade 3 or 4 non-hematologic or grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 4.0
时间窗: Up to 24 weeks
Will monitor toxicity of the personalized vaccines in using cohorts of size of 5, starting from the 1st patient using the Bayesian approach of Thall, Simon, Estey.
次要结局
- Persistence of an immune response defined by T cell interferon gamma release in response to selected personalized peptide antigens(Up to 24 weeks)
- Persistence of an immune response defined by levels of intracellular cytokine staining of T cells in response to stimulation with personalized peptide antigens(Up to 24 weeks)
- Persistence of an immune response defined by detection of antigen spreading(Up to 24 weeks)
- Time to progression(Up to 24 weeks)
- Persistence of an immune response defined by level of tetramer positive T cell population over time after T cell infusion(Up to 24 weeks)
- Proportion of patients who have received T cell infusion that is alive and progression free (complete response [CR] + partial response [PR] + stable disease) defined based on response criteria according to Response Evaluation Criteria in Solid Tumors 1.1(At 12 weeks post infusion)
- Response rate (CR + PR)(Up to 24 weeks)
- Overall survival(Up to 24 weeks)