A Phase 1/2 interventional study of CTLA-4/PD-1 antibodies expressing mesoCAR-T in Advanced Solid Tumor, sponsored by Shanghai Cell Therapy Research Institute. Status unknown at 1 site in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2017-06-09.
Sponsored by Shanghai Cell Therapy Research Institute · Phase 1/2, Interventional, and Treatment
This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting mesothelin (mesoCAR-T) in adult patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors.
This study will be conducted using a phase I/II trial design to assess the efficacy and safety of the CTLA-4 and PD-1 antibodies expressing mesothelin-CAR-T (mesoCAR-T) for patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors. MesoCAR-T can specificly and effectively kill the mesothelin positive cancer cells, CTLA-4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors.
The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells by leukapheresis, then activated and engineered to CTLA-4 and PD-1 antibodies expressing and chimeric antigen receptor targeting mesothelin. Cells are proliferated in culture and returned to the patients by venous transfusion. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's planned enrollment of 40 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Shanghai Cell Therapy Research Institute is the lead sponsor of 4 studies on the registry; none are open to participants now.
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Exclusion Criteria:
This study have only one arm that is the CTLA-4/PD-1 antibodies expressing mesoCAR-T cells group. All patients with advanced solid tumors will take part in the screening, who matching all the conditions will be chosen for the treatment.New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion.
Biological: CTLA-4/PD-1 antibodies expressing mesoCAR-T
Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing mesothelin-targeted CAR-T cells at (2-5) ×10\^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period.
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Determine treatment-related adverse events of the immunotherapy with common toxicity criteria for adverse effects (CTCAE) version 4.0.
Time frame: 2 years
The response evaluation of of the treatment for advanced solid tumors
The efficacy of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Time frame: 2 years
Progression free survival
Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.
Time frame: 2 years
Overall survival
Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
Time frame: 2 years
The quality of life as assessed by EORTC QLQ-30
The quality of life is assessed before and after the treatment by EORTC QLQ-30.
Time frame: 2 years
Proliferation and persistence of EGFR-CAR-T cells in peripheral blood
CAR-T proportion in peripheral blood of the patients is detected by flow cytometry assay to study the proliferation and persistence of mesothelin specific CAR-T cells.
Time frame: 6 months
CTLA-4 and PD-1 antibodies levels in peripheral blood
CTLA-4 and PD-1 antibodies levels are detected by ELISA assay to asess the expressing level of CTLA4 and PD-1 antibodies from CAR-T cells.
Time frame: 6 months
Plan to share: No
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This study is status unknown, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.
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Shanghai Cell Therapy Research Institute