Pilot Study of Autologous Chimeric Antigen Receptor Cells Against Mesothelin and CD19 in Patients With Pancreatic Cancer
试验速览
- 阶段
- 早期 1 期
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- The Percentage of Adverse Events (AEs) ≥ grade 3 assessed through MedDra and CTCAE v4.03 [Time frame: from infusion to 3 month afterward]
研究概览
简要总结
Pancreatic cancer patients receive chimeric antigen receptor (CAR) T cells against mesothelin (CARTmeso) or CD19 (CART19) cells administered at 3 days via pancreatic artery infusion or i.v. after preconditioning of cyclophosphamide. Both CART cells are autologous. CARTmeso cells target pancreatic cells which highly express mesothelin, while CART19 cells target tumor-associated B cells expressing cluster of differentiation antigen 19 (CD19) which are mostly immunosuppressive. The investigators hypothesize that this combination therapy may enhance the efficacy of CARTmeso cells in the body. Additionally, a medium dose of cyclophosphamide is used to enhance the engraftment of CART cells.
详细描述
This is a single arm, open-label, pilot study to determine the safety and feasibility of combination CARTmeso cells and CART19 cells in patients with pancreatic cancer following lymphodepletion with cyclophosphamide. Both cells contain CAR proteins consisting of a murine-derived single chain antibody fragment (scFv), cluster of differentiation antigen 137 (41BB) co-stimulatory domain and cluster of differentiation antigen 3 zeta chain (CD3ζ) signaling domain transduced by lentivirus
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •serum soluble mesothelin-related protein (SMRP) > 0.4 nanomolar/L
- •Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease
- •18 years of age and ≤65
- •Life expectancy greater than 3 months
- •Satisfactory organ and bone marrow function
排除标准
- •Participation in a therapeutic investigational study within 4 weeks prior to the screening visit
- •Active invasive cancer other than pancreatic cancer
- •HIV, hepatitis B/C virus, or infections
- •Active autoimmune disease requiring immunosuppressive therapy within 4 weeks
- •Planned concurrent treatment with systemic high dose corticosteroids
- •Patients requiring supplemental oxygen therapy
- •Pregnant or breastfeeding women
研究组 & 干预措施
CARTmeso/19 treatment arm
Patients with pancreatic cancer receiving CARTmeso and CART19 autologous cells via artery infusion or i.v. with cyclophosphamide precondition
干预措施: CARTmeso CART19 (Biological)
结局指标
主要结局
The Percentage of Adverse Events (AEs) ≥ grade 3 assessed through MedDra and CTCAE v4.03 [Time frame: from infusion to 3 month afterward]
时间窗: From first infusion to 3 months afterward
Primary outcome is the percentage of adverse events (AEs) ≥ grade 3. AEs are assessed through MedDra and CTCAE v4.03. Any patients who receive any dose of CART cells will be evaluated
次要结局
- Overall Response Rate defined as any improvement measured by imaging following RECIST 1.1 [Time Frame: Day 14 and 1 month after infusion](Day 14 and 1 month after infusion, or until patient withdraw consent or receive new therapy)
研究者
Meng-Tao Zhou
Director
First Affiliated Hospital of Wenzhou Medical University