This is a single-center, double-arm, open-label study. this study plans to evaluate the safety and efficacy of CD70-targeting CAR-T cells in the treatment of CD70-positive advanced/metastatic Gynecologic Cancer, and obtain recommended doses and infusion patterns.
The research designs to follow 2 groups:Intravenous infusion group and Intraperitoneal injection group;each group sets up 2 phases,the first phase is dose discovery phase to obtain recommended doses,the second phase is dose expansion phase to verify the safety in the recommended doses. In the discovery phase,each group puts up 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CD70-positive advanced/metastatic solid tumors.In the dose expansion phase,each group will choose one or two dose groups to verify the safety and efficacy at this dose,and plan to recruit about 6 subjects in each dose group.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
After lymphodepletion with Fludarabine and Cyclophosphamide,CAR T cells were transfused intravenically
After lymphodepletion with Fludarabine and Cyclophosphamide,CAR T cells were injected intraperitoneally
The First Affiliated Hospital of Wannan Medical College
Wuhu, Anhui, China
RECRUITINGIncidence of Adverse events after CD70 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 CD70 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 CD70 positive advanced malignancies [Effectiveness]
Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria),the minimum value is 0%,maximum value is 100%, and higher scores mean a better outcome.
Time frame: 3 months
Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
Objective response rate includes:The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria),the minimum value is 0%,maximum value is 100%, and higher scores mean a better outcome.
Time frame: 3 months
Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
Time frame: 2 years
Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
PFS will be assessed from the first CD70-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Time frame: 2 years
Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
OS will be assessed from the first CD70-CAR-T cell infusion to death from any cause (Assessed based on RECIST criteria)
Time frame: 2 years
AUCS of CD70 CAR-T cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
Time frame: 3 months
CMAX of CD70 CAR-T cells [Cell dynamics]
CMAX is defined as the highest concentration of CD70 CAR-T cells expanded in peripheral blood
Time frame: 3 months
TMAX of CD70 CAR-T cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Time frame: 3 months
Pharmacodynamics of CD70 CAR-T cells[Cell dynamics]
Concentration levels of CAR-T-related serum cytokines such as CRP, IL-6, ferritin at each time point,which measured by Chemiluminescence method
Time frame: 3 months
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