Safety and Activity of Programmed Cell Death-1 Knockout Engineered T Cells in Patients With Previously Treated Advanced Esophageal Squamous Cell Carcinoma: An Open-label, Single-arm Phase 1 Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Response Rate
研究概览
简要总结
This study will evaluate the safety of PD-1 knockout engineered T cells in treating advanced esophageal cancer. Blood or tissue samples will also be collected for research purposes.
详细描述
This is a prospective clinical study of ex-vivo selected, engineered, and expanded PD-1 knockout T cells from autologous origin. 16 advanced esophageal cancer patients are planned to receive two cycles of PD-1 knockout engineered T cells infusion. Immunological markers are analyzed as well.
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
盲法说明
open-label
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
- •Histologically confirmed recurrent or metastatic esophageal cancer
- •Measurable disease
- •Progressed after standard treatments
- •ECOG performance status of 0-2
- •Expected life span: >= 3 months
- •Toxicities from prior treatment has resolved or ≤ grade 1
- •Major organs function normally
- •Women at pregnant ages should be under contraception
- •Willing and able to provide informed consent
排除标准
- •Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ
- •Poor vasculature
- •Disease to the central nervous system
- •Blood-borne infectious disease, e.g. hepatitis B
- •History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
- •With other immune diseases, or chronic use of immunosuppressants or steroids
- •Pregnancy (women of childbearing potential:Refusal or inability to use effective means of contraception)
- •Breastfeeding
- •Decision of unsuitableness by principal investigator or physician-in-charge
研究组 & 干预措施
Experimental Group
Peripheral blood lymphocytes will be collected and Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and reinfused back into patients. To avoid allergic reactions, 50 mg hydrocortisone was intravenously injected into the patient 30 min before cells infusion every time. Best supportive care was also provided for patients.
A total of 1 to 10 x 10^9 PD-1 Knockout T cells will be infused each cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT or they withdrew consent.
干预措施: PD-1 Knockout T Cells (Other)
结局指标
主要结局
Response Rate
时间窗: 1-3 months
Response will be evaluated according to RECIST v1.1
次要结局
- Incidence of Treatment-Emergent Adverse Events(6 months)
研究者
Shixiu Wu
Professor
Hangzhou Cancer Hospital