Clinical Study of Redirected Autologous T Cells With a Claudin18.2-targeted Chimeric Antigen Receptor in Patients With Advanced Gastric Adenocarcinoma and Pancreatic Adenocarcinoma
试验速览
- 阶段
- 不适用
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety and tolerance
研究概览
简要总结
A single arm, open-label pilot study is designed to determine the safety, tolerability and engraftment of CAR-CLD18 T cells in patients with advanced gastric adenocarcinoma and pancreatic adenocarcinoma.
详细描述
For patients with gastric adenocarcinoma who have not been cured with first line chemotherapy, and who are not willing to undergo second line chemotherapy after the failure of first line chemotherapy while there are no effective therapies for their unmet medical needs known at this time, and for patients with advanced/metastatic pancreatic adenocarcinoma which has relapsed after surgery or for which there is no surgical indication, who have not been cured with or refused to receive other standard regimens, single or multiple doses of CAR-CLD18 T cells will be given to observe safety and efficacy of CAR-CLD18 T cells.
Primary objectives:
Determine the safety, tolerability and cytokinetics of the autologous T cells transduced with anti-Claudin18.2 lentiviral vector in patients with gastric adenocarcinoma and pancreatic adenocarcinoma.
Secondary objectives:
Make a preliminary evaluation on the efficacy of CAR-CLD18 T cells in patients with gastric adenocarcinoma and pancreatic adenocarcinoma with the following parameters:
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
- •Patients aged 18 - 70 with pathologically confirmed advanced gastric adenocarcinoma and pancreatic adenocarcinoma.
- •Biopsy confirmation of Claudin18.2 positive.
- •Patients with advanced gastric adenocarcinoma who have not been cured with second line chemotherapy, and who are not willing to undergo second line chemotherapy after the failure of first line chemotherapy. (1) Failure of treatment is defined as disease progression, recurrence or metastatic disease, or intolerable toxicities occurred after treatment. (2) Each line of treatment during the period of disease progression includes one or more chemotherapy drugs which are administered for not less than one cycle or even longer. Neoadjuvant/adjuvant therapy can be applied at an earlier stage of treatment. If patient has developed recurrence or metastatic disease within 24 weeks of neoadjuvant/adjuvant therapy, it is considered as one line of systemic chemotherapy. (3) Therapies that can be performed at an earlier stage are chemotherapy in conjunction with molecular targeted drugs.
- •Patients with advanced/metastatic pancreatic adenocarcinoma which has relapsed after surgery or for which there is no surgical indication, who have not been cured with or refused to receive other standard regimens.
- •Expected survival after first dose of study drug > 12 weeks.
- •At least one measurable lesion (≥ 10 mm) for imaging assessment.
- •ECOG scores 0 -
- •Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
- •White blood cells (WBCs) ≥ 2.5×10^9/L Platelets (PLT) ≥ 100×10^9/L Hemoglobin, Blood (Hb) ≥ 9.0 g/dL MID ≥ 1.5×10^9/L Lymphocyte (LY) ≥ 0.47×10^9/L LY% ≥ 15%
- •Serum albumin (Alb) ≥ 30 g/L
- •Serum lipase (LPS) and serum amylase < 1.5 ULN
- •Serum creatinine ≤ 1.5 ULN
- •Alanine aminotransferase (ALT) ≤ 2.5 ULN Aspartate aminotransferase (AST) ≤ 2.5 ULN If osseous metastasis or liver metastasis is developed and alkaline phosphatase (ALP) > 2.5 ULN, ALT and AST < 1.5 ULN.
- •Serum total bilirubin (TBIL) ≤ 1.5 ULN
- •Prothrombin Time (PT): International Normalized Ratio (INR) < 1.
- •PT < (ULN + 4) s
- •All test results should be within their normal ranges, and the patient is not receiving continuous supportive care.
排除标准
- •Patients with any of the following conditions are not eligible for the study.
- •Pregnant or lactating women.
- •HIV positive, HCV positive, HBV DNA copies ≥ 10^
- •Uncontrolled active infection.
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- •Allergic to immunotherapies and related drugs.
- •Untreated brain metastases or having symptoms of brain metastases.
- •Metastases to the lung: central tumor or multiple metastases.
- •Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
- •Patients with unstable or active peptic ulcer or with alimentary tract hemorrhage.
- •Patients with previous organ transplantation or in preparation for organ transplantation.
- •Patients in need of anticoagulant treatment (e.g. warfarin or heparin).
- •Patients in need of long-term antiplatelet treatment (aspirin, dosage > 300 mg/d; clopidogrel, dosage > 75 mg/d).
- •Previous treatment with chemoradiotherapy and tumor-targeting drug which were conducted 4 weeks prior to the study (blood collection).
- •Patients have undertaken major surgeries or have been badly injured 4 weeks before the study (blood collection), or will undertake major surgeries during the study.
- •The judgment of investigators that the patient is not able to or not willing to follow the instructions of the protocol.
研究组 & 干预措施
CAR-CLD18 T cells
Autologous T Cells with a Claudin18.2-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection.
Lymphodepletion conditioning regimen will be applied prior to CAR-CLD18 T cell infusion.
干预措施: CAR-CLD18 T Cells (Genetic)
结局指标
主要结局
Safety and tolerance
时间窗: 24 weeks
During the trial conduction, especially within the 24 weeks of treatment phase when CAR-CLD18 T cell administered, all adverse events (including laboratory abnormality and clinical events) will be closely monitored, and all ≥ grade 3 adverse events per CTCAE (v 3.0) will be recorded, including but not limited to the toxicities potentially suspected to relate to infusion procedures and/or CAR-CLD18 T cell therapy as listed below: * Fever * Chills * Nausea, vomiting and other gastrointestinal symptoms * Fatigue * Hypotension * Respiratory distress * Tumor lysis syndrome * Cytokine release syndrome * Neutropenia, thrombocytopenia * Liver and kidney dysfunction
次要结局
- Engraftment(2 years)
研究者
Bin Wang
Attending physician
Changhai Hospital