Phase 1b Study of the Efficacy and Safety of CAR2 Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases Resistant to Standard Therapy Using the HITM Method and Pressure Enabled Delivery Device
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Assess preliminary efficacy by overall survival
研究概览
简要总结
This study is an open-label, single arm phase 1b safety study of CAR2 Anti-CEA CAR-T cell hepatic arterial infusions for pancreatic carcinoma patients with carcinoembryonic antigen positive (CEA+) liver metastases resistant to standard therapy who meet all other eligibility criteria.
详细描述
Patients will receive weekly 3 doses of CAR2 Anti-CEA CAR-T cells in each 28-day cycle by hepatic arterial infusions using a Pressure Enhanced Delivery Device (PEDD) with low dose systemic IL-2 support. Patients may receive up to 3 cycles of CAR2 Anti-CEA CAR-T cell hepatic arterial infusions, per discretion of the investigator.
All patients who receive investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.
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
- •Must have documented CEA+ pancreatic adenocarcinoma liver metastases and have failed greater than or equal to 1 line of conventional systemic therapy.
- •Must have at least evaluable liver metastases.
- •Must have a life-expectancy at least 12 weeks.
- •Patients must be willing and able to comply with the study schedule and all other protocol requirements.
- •Females of childbearing potential must have 2 negative pregnancy tests, agree to pregnancy tests during the study, and sexually active female and male patients must be willing to use an effective birth control method to avoid pregnancy.
排除标准
- •Subjects who have received an investigational study drug within 14 days of leukapheresis or 28 days before receiving first dose of study drug.
- •Subjects who have received any approved anticancer medication within 14 days of leukapheresis or 14 days before receiving the first dose of study drug.
- •Have any unresolved toxicity greater than Grade 2 from previous anticancer therapy.
- •Have a history of confirmed metastases outside the peritoneal cavity, lungs, or liver.
- •More than 50% replacement of one or both liver lobes with tumor.
- •Has tumor causing biliary obstruction not amenable to stenting.
- •Have a high volume of lung or peritoneal metastases.
- •Has received any CAR cell line therapies.
- •Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts at screening.
- •Has untreated or ongoing intra-abdominal infection or bowel obstruction.
- •Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome), and alkaline phosphatase at screening regardless of causality.
- •Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
- •Female patients who are pregnant or breastfeeding.
- •Have active bacterial, viral, or fungal infections.
- •Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent study participation.
- •Left ventricular ejection fraction (LVEF) < 40%.
结局指标
主要结局
Assess preliminary efficacy by overall survival
时间窗: 6 months
As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.
次要结局
- Assess preliminary efficacy by serologic response rates by CA 19-9 levels(6 months)
- Assess preliminary efficacy by in-liver progression free survival (PFS)(6 months)
- Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)(6 months)
- Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)(6 months)
- Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens(6 months)
- Assess preliminary efficacy by duration of response in accordance with RECIST criteria(6 months)
- Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)(6 months)
- Assess preliminary efficacy by serologic response rates by CEA levels(6 months)