Trial of Second Generation Designer T Cells in Colorectal Carcinoma
The purpose of this study is to collect data on the safety and effectiveness of 2nd generation designer T cells in patients with colorectal cancer. Designer T cells are prepared by collecting white blood cells from the participant, and then modifying these cells in the laboratory so that they recognize the tumor antigen (CEA). These modified cells are then given back into the participant so that they can attack and kill tumor cells.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II/Pilot Trial of Second Generation Designer T Cells in Colorectal Cancer|
- Determine the safety of using modified T cells by documenting the type and severity of any side effects and establishing the Maximum Tolerated Dose (MTD). [ Time Frame: 1 Month ] [ Designated as safety issue: Yes ]
- Tumor Response [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
- Pharmacokinetics [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
- Pharmacodynamics [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Experimental: Gene Modified T Cells
Modified T cells
Biological: Gene Modified T Cells
One time infusion Modified T-Cells given through a vein in the arm or a catheter over a 30-60 minute period.
T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remissions of cancer. However, T cells are easily tolerized to self or tumor antigens and "immune surveillance" has manifestly failed in every cancer that is clinically apparent. It is the goal of this study to supply the specificities and affinities to patient T cells without regard for their "endogenous" T cell receptor repertoire, directed by antibody-defined recognition to kill malignant cells based on their expression of antigen. We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity, the hallmarks of an effective, self-sustaining immune response.
It therefore becomes of paramount interest to extend these studies to a human system of widespread clinical relevance to explore the clinical potential of this new technology. The target antigen for these studies is carcinoembryonic antigen (CEA), which is prominently expressed on tumors of the stomach, colon and rectum, breast, pancreas and other sites. Patients receive a single dose of gene-modified autologous T cells on this dose-escalation trial. Doses are 10^9, 10^10 and 10^11 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.
|United States, Rhode Island|
|Roger Williams Medical Center|
|Providence, Rhode Island, United States, 02908|
|Principal Investigator:||Richard P Junghans, PhD, MD||Roger Williams Medical Center|