Study of Autologous T-cells Redirected to Mesothelin With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Safety of CART-meso infusion: number of adverse events
研究概览
简要总结
This is a study in which pancreatic cancer patients receive a immunotherapy with CART-meso cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains.The lymphodepletion with cyclophosphamide may prolong the persistence of CART cells.
详细描述
This study is being conducted to assess the safety and efficacy of immunotherapy with CART-meso cells in dose escalation design. The trial will begin in Cohort 1 and progress to Cohorts 2, depending upon dose limiting toxicity (DLT) assessment .
Subjects will be enrolled serially, but infusions will be staggered to allow assessment of DLTs for determination of cohort progression, expansion, or dose de-escalation.
Cohort 1 subjects will receive a single dose of 1-3x10^7 /m^2 lentiviral transduced CART-meso cells after conditioning chemotherapeutic regimen.
Cohort 2 subjects will receive a single dose of 1-3x10^8 /m^2 lentiviral transduced CART-meso cells cells after conditioning chemotherapeutic regimen.
Dose limiting toxicity is defined as any adverse reactions at level 3 or above that may be associated with CART-meso within 4 weeks after infusion.
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
- •Signed informed consent
- •Unresectable or metastatic pancreatic cancer
- •Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease
- •18 - 70 years of age
- •ECOG performance status of 0 or 1
- •Life expectancy greater than 3 months
- •Satisfactory organ and bone marrow function
- •Meets blood coagulation parameters
- •Male and Female subjects of reproductive potential agree to use approved contraceptive methods
排除标准
- •Participation in a therapeutic investigational study within 4 weeks prior to the screening visit
- •Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion
- •Active invasive cancer other than pancreatic cancer
- •HIV, HCV, or HBV infections
- •Active autoimmune disease requiring immunosuppressive therapy within 4 weeks prior to screening visit, with exception of thyroid replacement
- •Ongoing or active infection
- •Planned concurrent treatment with systemic high dose corticosteroids
- •Patients requiring supplemental oxygen therapy
- •Prior therapy with gene modified cells
- •Previous experimental therapy with SS1 moiety, murine or chimeric antibodies
- •History of allergy to murine proteins
- •History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- •Clinically significant pericardial effusion, CHF, or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study
- •Pregnant or breastfeeding women
研究组 & 干预措施
CART-meso cells
A single dose of CART-meso T cells will be administered intravenously.The dose is 1-3×10^7/m^2 CART positive cells(chort 1)or 1-3×10^8/m^2 CART positive cells(chort 2).
干预措施: CART-meso cells (Biological)
结局指标
主要结局
Safety of CART-meso infusion: number of adverse events
时间窗: 60 months
Number of Adverse Events evaluated with NCI CTC AE, version 4.0\[Safety evaluation\]
次要结局
- Clinical response of CART-meso(60 months)
- CAR-T cell detection(60 months)