Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer
|Breast Cancer||Biological: Gene Modified T Cells Biological: Gene Modified T Cells and Interleukin 2||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer|
- Phase Ia: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 ]
- Phase Ib: Determine optimal biologic dose (OBD) in terms of value of added interleukin 2. [ Time Frame: 1 Month ]
- Tumor Response [ Time Frame: 1 Month ]
- Pharmacokinetic [ Time Frame: 1 month ]
- Pharmacodynamic [ Time Frame: 1 Month ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
|Experimental: Phase Ia||
Biological: Gene Modified T Cells
Gene Modified T Cells Phase Ia: One time infusion Modified TCells given through a vein in the arm or a catheter over a 30-60 minute period
|Experimental: Phase Ib: Control||
Biological: Gene Modified T Cells and Interleukin 2
One time infusion Modified T Cells without or with (randomized) continuous infusion outpatient interleukin 2 (IL2) for two weeks
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.
For the Phase Ia component, patients receive a single dose of gene-modified autologous T cells on this dose-escalation trial. Doses are 10^9 and 10^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.
For the Phase Ib component, patients receive a fixed dose of gene-modified T cells (10^11 cells), randomized to receive T cell growth factor interleukin 2 (+IL2) [Experimental] or not (-IL2) [Control]. The IL2 is administered outpatient by continuous infusion for a two-week period. On Day +2 and Day +10, the patient's tumor is biopsied to assess the designer T cell presence in the tumor as a means of judging the benefit of added IL2. Patients will also be followed for tumor response.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00673829
|United States, Massachusetts|
|Tufts University Medical Center|
|Boston, Massachusetts, United States, 02115|
|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|