CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for MUC1 Positive Advanced Solid Tumor
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|ClinicalTrials.gov Identifier: NCT03179007|
Recruitment Status : Unknown
Verified June 2017 by Shanghai Cell Therapy Research Institute.
Recruitment status was: Recruiting
First Posted : June 7, 2017
Last Update Posted : June 7, 2017
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumor||Biological: Anti-CTLA-4/PD-1 expressing MUC1-CAR-T||Phase 1 Phase 2|
This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T for patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors. MUC1-CAR-T can specificly and effectively kill the MUC1 positive cancer cells, CTLA4 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 (PBMC) by leukapheresis, and then activated and engineered to express CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting MUC1. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for Patients With MUC1 Positive Advanced Solid Tumors|
|Estimated Study Start Date :||June 7, 2017|
|Estimated Primary Completion Date :||January 20, 2019|
|Estimated Study Completion Date :||April 20, 2019|
Experimental: Anti-CTLA-4/PD-1 expressing MUC1-CAR-T
This study have only one arm that is anti-CTLA-4/PD-1 expressing MUC1-CAR-T group. All patients with advanced solid tumor will take part in the screening, who matching all the conditions will be chosen for the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells. New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion.
Biological: Anti-CTLA-4/PD-1 expressing MUC1-CAR-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 MUC1 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.
Other Name: CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells
- Safety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells [ Time Frame: 2 years ]Determine the toxicity profile of CTLA4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
- The efficacy of the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells for advanced solid tumors [ Time Frame: 2 years ]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).
- Progression free survival [ Time Frame: 2 years ]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.
- Overall survival [ Time Frame: 2 years ]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.
- Change of life quality [ Time Frame: 2 years ]Life quality is assessed before and after the treatment.
- Proliferation and persistence of MUC1 specific CAR-T cells in peripheral blood of the patients after treatment [ Time Frame: 6 months ]CAR-T proportion in peripheral blood of the patients is detected by flow cytometry assay to study the proliferation and persistence of MUC1 specific CAR-T cells.
- CTLA-4 and PD-1 antibodies level in peripheral blood of the patients after treatment [ Time Frame: 6 months ]CTLA-4 and PD-1 antibodies level are detected by ELISA assay to asess the expressing level of CTLA4 and PD-1 antibodies from CAR-T cells.
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): NCT03179007
|Contact: Zhiwei Zhang, Ph.Dfirstname.lastname@example.org|
|Ningbo No.5 Hospital (Ningbo Cancer Hospital)||Recruiting|
|Ningbo, Zhejiang, China, 315201|
|Contact: Bi Wang 0086-0574-86689113 email@example.com|
|Principal Investigator: Jiangtao Wang|
|Study Chair:||Qijun Qian, Ph.D||Shanghai Cell Therapy Research Institute|
|Study Chair:||Huajun Jin, Ph.D||Shanghai Cell Therapy Research Institute|
|Study Director:||Zhiwei Zhang, Ph.D||Shanghai Cell Therapy Research Institute|
|Study Director:||Yan Sun||Shanghai Cell Therapy Research Institute|
|Principal Investigator:||Jiangtao Wang||Ningbo No.5 Hospital(Ningbo Cancer Hospital)|