Autologous Redirected RNA Meso-CIR T Cells
To determine the safety and manufacturing feasibility of IV autologous chimeric immune receptor (CIR) T cells transfected with anti-mesothelin messenger RNA (mRNA) expressing a single chain antibody variable fragment linked to the intracellular CD 3 zeta T cell receptor domain and the 4-1BB costimulatory domain.
|Study Design:||Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||Phase 1 Clinical Trial of Autologous Mesothelin Re-Directed T Cells Administered Intravenously in Patients With Progressive Malignant Pleural Mesothelioma|
- Adverse Events [ Time Frame: Until week 4 ] [ Designated as safety issue: Yes ]Occurence of study related adverse events greater than to equal to Grade 3 events that are possibly, likely or definitely related to study treatment.
- Clinical response Rate [ Time Frame: through 6 months post dosing ] [ Designated as safety issue: Yes ]Effect of CIR T cell infusion on systemic adaptive and innate immunity
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
|Experimental: Cohort 1 - One dose of cells||Biological: Autologous T cells|
|Experimental: Cohort 2 - three doses of cells||Biological: Autologous T cells|
The purpose of this study is to test the safety of infusing the study product CIR T cells. These T cells are made using T cells obtained through apheresis and introducing the T cells to a temporary gene which will cause them to start making a new type of antibody that will attach mesothelin (this antibody is found on the surface of the cancer cells). In theory, once the modified T cells attach to mesothelin, the cells will be activated to stimulate the subject's own immune system to attack the mesothelin cells. This type of modified cell is called a T cell transduced transfected with chimeric anti-mesothelin immunoreceptor. Subjects will be enrolled serially with all subjects receiving 1xe8 to 1x1e9 modified CIR T cells every other day for 3 infusions. Each patient will be observed for 9 days for toxicity assessment prior to receiving a second cycle of modified CIR T cells every other day for 3 infusions. The preceding subject must have completed the two-cycle regimen and been observed for toxicity through day 21 before the next subject can be enrolled.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01355965
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|