A Phase I Clinical Trial of PD-1 Knockout Engineered T Cells Treating Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of Dose of PD-1 Knockout T Cells Using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in Patients
研究概览
简要总结
This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic non-small cell lung cancer. Blood samples will also be collected for research purposes.
详细描述
This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Pathologically verified stage IV non-small cell lung cancer with measurable lesions (On CT: longest diameter of tumoral lesion >=10 mm, shorted diameter of lymph node >=15 mm; measurable lesions should not have been irradiated)
- •Progressed after all standard treatment
- •Performance score: 0-1
- •Expected life span: >= 6 months
- •Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy
- •Major organs function normally
- •Women at pregnant ages should be under contraception
- •Willing and able to provide informed consent
排除标准
- •Pathology is mixed type
- •Emergent treatment of tumor emergency is needed
- •Poor vasculature
- •Coagulopathy, or ongoing thrombolytics and/or anticoagulation
- •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
- •Compliance cannot be expected
- •Other conditions requiring exclusion deemed by physician
研究组 & 干预措施
A - Two cycles
Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) 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 infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.
A total of 1 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.
干预措施: Cyclophosphamide (Drug)
A - Two cycles
Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) 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 infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.
A total of 1 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.
干预措施: PD-1 Knockout T Cells (Other)
B- Two cycles
Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) 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 infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.
A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.
干预措施: Cyclophosphamide (Drug)
B- Two cycles
Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) 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 infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.
A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.
干预措施: PD-1 Knockout T Cells (Other)
C- Two cycles
Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) 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 infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.
A total of 4 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.
干预措施: Cyclophosphamide (Drug)
C- Two cycles
Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) 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 infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.
A total of 4 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.
干预措施: PD-1 Knockout T Cells (Other)
结局指标
主要结局
Number of Participants With Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of Dose of PD-1 Knockout T Cells Using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in Patients
时间窗: Dose Escalation - Approximately 6 months
次要结局
- Number of Patients With Overall Response(3 months)
- Tumor Necrosis Factor-a Change in the Peripheral Blood.(Baseline, 1 month and 3 month)
- Progression Free Survival (PFS)(The time from the date of first edited T cell infusion to the date of disease progression or death due to any reason.)
- Number of Participants With Genes Mutations in Peripheral Blood Circulating Tumor DNA (ctDNA)(Baseline)
- Interleukin-10 Change in the Peripheral Blood.(Baseline, 1 month and 3 month)
- Number of Patients With Disease Control at 8 Weeks(8 weeks)
- Overall Survival (OS)(The duration from date of first edited T cell infusion to the date of death due to any reason)
- Interleukin-6 Change in the Peripheral Blood.(Baseline, 1 month and 3 month)
研究者
You Lu
Chair of Department of Thoracic Cancer
Sichuan University