Clinical Study on the Efficacy and Safety of c-Met/PD-L1 CAR-T Cell Injection in the Treatment of HCC
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|ClinicalTrials.gov Identifier: NCT03672305|
Recruitment Status : Not yet recruiting
First Posted : September 14, 2018
Last Update Posted : September 18, 2018
Title: Single-center, open clinical study on the efficacy and safety of c-Met/PD-L1 T cell injection in the treatment of primary hepatocellular carcinoma
Stage: Phase I clinical trial
Purpose: To evaluate the efficacy and safety of c-Met/PD-L1 CAR-T cells in patients with primary hepatocellular carcinoma
Object: patients with primary hepatocellular carcinoma
Sample size: 50 cases
Number of centres：1
Study design: CT, MRI, PET and blood biochemical tests were performed before treatment to evaluate the state of HCC. Peripheral blood of the patient was extracted and PBMC was isolated. CAR-T cells were obtained by tranducing PBMC with c-Met/PD-L1 CAR lentivirus, and the proliferation capacity and immune phenotype of the cells were tested. After passing the inspection, the cells were re-injected into the patient three times. The efficacy and safety of c-Met/PD-L1 CAR-T cells was assessed respectively at 4 week, 12 week, 24 week and 48 week after treatment.
Trial product: c-Met/PD-L1 CAR-T cells
Course of treatment: 3 days for a course of treatment, only one course of treatment. A second course is given as appropriate if the treatment is beneficial to the patient.
|Condition or disease||Intervention/treatment||Phase|
|Primary Hepatocellular Carcinoma||Biological: c-Met/PD-L1 CAR-T cell injection||Early Phase 1|
Hide Detailed Description
Title: Single-center, open clinical study on the efficacy and safety of c-Met/PD-L1 CAR-T cell injection in the treatment of primary hepatocellular carcinoma
To evaluate the efficacy of c-Met/PD-L1 CAR-T cell injection in the treatment of primary hepatocellular carcinoma.
- To evaluate the clinical safety of c-Met/PD-L1 CAR-T cell injection in the treatment of primary hepatocellular carcinoma;
- To assess the amplification and persistence of c-Met/PD-L1 CAR-T cells in subjects.
Study design:Single center, open clinical study
Subjects:Patients with primary hepatocellular carcinoma
Clinical trial cycle:
Screening stage:Selecting enrolled patients and collecting peripheral mononuclear cells; Treating stage: Pretreating and the backtransfusing c-Met/PD-L1 CAR-T cells Follow-up stage:Treatment was observed for 28 days (short-term follow-up), 28 days to 24 weeks (mid-term follow-up), and 24 weeks to progression/death (long-term follow-up);
Trial product:c-Met/PD-L1 CAR-T cells Dosage:The backtransfusion dose was determined by the investigator based on the subject's own/disease condition and in vitro preparation (recommended dose: 2 * 10^6/kg); Infusion way:Steady intravenous drip within 15 to 30 minutes
Clinical trial procedure:
The screening period:
The subjects signed the informed consent form and performed a series of examinations according to the interview flow chart. The researchers judged whether the subjects met the inclusion criteria according to the examination results and inclusion/exclusion criteria, and did not meet the exclusion criteria. If the subjects were enrolled, peripheral blood mononuclear cells were collected, and the collection standard was 2-4 * 10^8 white blood cells;
nonmyeloablative pretreatment:(The following options are selected on a case-by-case basis)
- Fludarabine+Cyclophosphamide (FC)
- Bis-1-nitrosourea+Etoposide+Arabinoside+Cyclophosphamide (BECA);
The specific time and dose of retransfusion can be determined by the researchers;
Short-term follow-up period:
Subjects will undergo a series of examinations according to the visit flow chart within 28 days after the expected dose of c-Met/PD-L1 CAR-T cells injection.The short-term efficacy and safety of c-Met/PD-L1 CAR-T cells injection were evaluated by the researchers based on the test results.
Subjects will undergo a series of examinations according to the visit flow chart 28 days to 24 weeks after re-transfusion of c-Met/PD-L1 CAR-T cells injection.The researchers will evaluate the mid-term efficacy and safety of c-Met/PD-L1 CAR-T cells based on the test results.
Subjects will undergo a series of examinations according to the visit flow chart 24 weeks later until progress or death after retransfusion of c-Met/PD-L1 CAR-T cells.The long-term efficacy and safety of c-Met/PD-L1 CAR-T cells will be evaluated according to the test results.
- Withdrawal visit (at any time) :All subjects may withdraw from this study at any stage of the trial.If the subjects withdraw from the study after returning to the c-Met/PD-L1 CAR-T cells, they shall complete the inspection items required in the visit flow chart, and the reason for the withdrawal shall be recorded in detail by the researchers.If the subject passes screening but withdraws from the visit before returning to the c-Met/PD-L1 CAR-T cells, only the baseline and screening tests need to be completed, and the reason for withdrawal will be recorded in detail by the investigators.If the subject withdraws from the screening test before the end of the screening test, only the screening test shall be completed and the reason for withdrawal shall be recorded in detail by the investigators.If treatment is discontinued due to adverse reactions (AE), the investigators will follow up with the necessary safety until the subjects return to baseline or to a stable state.
Evaluation index Main evaluation index
- Objective tumor remission rate (ORR),complete remission (CR) and partial remission (PR) at 4 weeks, 12 weeks, 24 weeks and 48 weeks after treatment with c-Met/PD-L1 CAR-T cells;
- Overall survival
- Progression free survival
- Event-free survival
Secondary evaluation index
- Incidence of treatment-related adverse events (level 3 or level 4 adverse reactions, CTCAE V4.03 criteria). These included adverse events related to the treatment of c-Met/PD-L1 CAR-T cells, severe adverse events and clinically significant laboratory abnormalities;
- The amplification level of c-Met/PD-L1 CAR-T cells in the subjects varied with time;
- Duration of c-Met/PD-L1 CAR-T cells in the subjects;
- The abatement features of hepatocellular carcinoma in subjects.
Statistical analysis SPSS18.0 was used for statistical analysis
- The primary and secondary end points were analyzed by intentionality. The statistical analysis method of the end point was used to describe tumor ORR according to different follow-up time. Kaplan-meier method and survival curve were used to describe OS, PFS and EFS
- The statistical analysis method of the secondary study endpoint was to describe the occurrence number and incidence of treatment-related adverse events, and to compare the difference of vital signs and laboratory indexes before and after treatment
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Single-center, Open Clinical Study on the Efficacy and Safety of c-Met/PD-L1 Chimeric Antigen Receptor T Cell Injection in the Treatment of Primary Hepatocellular Carcinoma|
|Estimated Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||October 30, 2019|
|Estimated Study Completion Date :||October 30, 2019|
c-Met/PD-L1 CAR-T cells treating group
Intervention Name:c-Met/PD-L1 CAR-T cell injection dosage form: injection dosage:The backtransfusion dose (recommended dose: 2 * 10^6/kg) was determined by the investigator based on the subject's own/disease condition and in vitro preparation.
Biological: c-Met/PD-L1 CAR-T cell injection
injection content:c-Met/PD-L1 CAR-T cell Infusion way:Steady intravenous drip in 15 to 30 minutes
- The efficacy of c-Met/PD-L1 CAR-T cells in the treatment of HCC [ Time Frame: 6 months after treatment ]assessing the efficacy of c-Met/PD-L1 CAR-T cells through overall survival
- the incidence of treatment-emergent adverse events of c-Met/PD-L1 T cell injection in the treatment of HCC [ Time Frame: 6 months after treatment ]the level 3 or level 4 adverse reactions according to CTCAE V4.03 standard
- The amplification and persistence of c-Met/PD-L1 CAR-T cell in the subjects varied with time [ Time Frame: 6 months after treatment ]The amplification level of c-Met/PD-L1 CAR-T cells varied with time and the duration of anti-c-met/pd-l1 CAR-T cells in the subjects
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03672305
|Contact: Guozhong Ji, archiater||+86-13951031818||J58430@njmu.edu.cn|
|Study Chair:||Guozhong Ji, archiater||Second affiliated hospital of nanjing medical university|