Phase II/Pilot Study of 2nd Generation Anti-CEA Designer T Cells in Adenocarcinomas
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 remis-sions 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 these studies 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. This extends the approach of Anderson, Rosenberg and co-workers to introduce or augment expression of genes in patients' T cells in a therapeutic setting.
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 predominantly expressed on tumors of the colon and rectum, breast, pancreas and other sites.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||"Phase II/Pilot Study of 2nd Generation Anti-CEA Esigner T Cells in Adenocarcinomas"|
- Efficacy [ Time Frame: 24 months ] [ Designated as safety issue: No ]Monitoring of CEA levels, pre and post infusion of T cells. Monitoring of CT and PET scans pre and post infusion.
- Safety [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Monitoring and recording of all adverse and serious adverse events using CTC 4.0 criteria.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Experimental: 2nd Generation Designer T Cells
All participants will receive gene modified T cells, with concomitant IL2 for 30 days post infusion.
Genetic: Gene Modified T Cells
Subjects will undergo T cell leukopheresis. The collected T cells will be genetically modified, and then re-infused peripherally. IL2 will be given concomitantly for 30 days post modified T cell infusion via CADD pump.
Other Name: 2nd Generation Designer T Cells
CEA is perhaps the most prominent tumor marker among malignancies of epithelial origin: colorectal carcinoma, with 60-94% of tumors positive in patients with advanced disease; breast carcinoma, with 30-60% of metastatic cases positive for CEA; and cancers of the lung, liver, pancreas, head and neck, bladder, cervix and prostate with 30% or more with CEA+ tumors.
The application of these therapies in the four Phase II/Pilot clinical sub studies listed below proceed after collecting patient lymphocytes by leukapheresis, which are then modified by transfer of the chimeric gene for Ig-CD28-TCRzeta. Cells are selected in culture with amplification and activation of the now-specific anti-tumor T cells. These are then re infused into the patients, with IL2 supplementation, and toxicity and response are monitored.
There are four sub studies embedded within this Phase II Study of Second Generation Designer T Cells in CEA-expressing Adenocarcinomas. The embedded studies are:
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Gastric Cancers (CEA-G)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Colorectal Cancers (CEA-C)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Lung Cancers (CEA-L)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Solid Tumors (CEA-S)
A total of 12 subjects per protocol or a total of 48 subjects will be enrolled combining the enrollment of the 4 CEA-expressing protocols.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01723306
|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|