This trial is an open-label, single-arm clinical study. The main purpose is to verify the safety and efficacy of CAR-T cell preparations in the treatment of CEA-positive advanced malignant tumors, and to obtain the recommended dose and infusion scheme of CAR-T cell preparations for the treatment of patients with CEA-positive advanced malignant tumors.
Carcinoembryonic antigen (CEA) is a classic tumor marker, which is positively expressed in a variety of digestive tract tumors. In normal tissue cells, only a small amount of CEA is expressed in the cell membrane of digestive tract cells. In the early clinical trials of CAR-T targeting CEA carried out by the technical partner, it was found that CAR-T cell preparations have a certain killing effect on CEA-positive tumor cells. At the same time, no serious CAR-T-related adverse events were found through dose-escalating infusion. In this study, through the optimization of the CAR structure and the improvement of the culture method, the killing ability and survival ability of the CAR-T cell preparation on tumor cells in vitro and in vivo were improved to further verify the safety and efficacy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Administration method: intravenous infusion or intraperitoneal injection; Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.
Shandong Second Provincial General Hospital
Jinan, Shandong, China
RECRUITINGIncidence of Adverse events after CEA-CAR-T cells infusion [Safety and Tolerability]
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
Time frame: 28 days
Obtain the maximum tolerated dose of CEA-CAR-T cells[Safety and Tolerability]
Dose-limiting toxicity after cell infusion
Time frame: 28 days
Disease control rate of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]
Disease control rate: including CR, PR and SD
Time frame: 3 months
Changes in serum tumor markers of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]
Changes in serum tumor markers:CEA、 CA199、 CA125
Time frame: 3 months
AUCS of CEA-CAR-T cells [Cell dynamics]
AUCS is defined as the area under the curve in 28 days and 90 days
Time frame: 1 years
CMAX of CEA-CAR-T cells [Cell dynamics]
CMAX is defined as the highest concentration of CEA-CAR-T cells expanded in peripheral blood
Time frame: 1 years
TMAX of CEA-CAR-T cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Time frame: 1 years
Pharmacodynamics of CEA-CAR-T cells[Cell dynamics]
The content of free CEA in peripheral blood at each time point measured by Chemiluminescence immunoassay
Time frame: 1 years
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