CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells (HITM)
|ClinicalTrials.gov Identifier: NCT01373047|
Recruitment Status : Completed
First Posted : June 14, 2011
Last Update Posted : July 30, 2013
|Condition or disease||Intervention/treatment||Phase|
|Liver Metastases||Biological: anti-CEA 2nd generation designer T cells||Phase 1|
T cells have the power to destroy malignant cells under certain conditions, as demonstrated by the rare spontaneous remissions of cancer. However, the endogenous T cell response to cancer fails in the vast majority of patients and the tolerogenic conditions within the liver may pose additional immunologic barriers for those with intrahepatic metastases. The investigators modify patient T cells to kill malignant cells based on their expression of tumor antigens using antibody-defined recognition. The investigators 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.
The present trial will test the regional infusion of anti-CEA designer T cells, given via the hepatic artery using a percutaneous approach. This is an intra-patient dose escalation trial, where patients will receive three doses over the course of six weeks. Doses are 10^8, 10^9 and 10^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases|
|Study Start Date :||June 2011|
|Primary Completion Date :||July 2013|
|Study Completion Date :||July 2013|
|Experimental: Intrahepatic anti-CEA designer T cells||
Biological: anti-CEA 2nd generation designer T cells
Three infusions of gene-modified T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach.
- Determine the safety of modified T cells delivered into the hepatic artery by documenting the type and severity of any side effects and establishing the Maximum Tolerated Dose (MTD). [ Time Frame: 1 month ]
- Tumor Response by CT or MRI and PET scan [ Time Frame: 1 month ]CT or MRI and PET imaging will be obtained before the first infusion and following the final infusion to document changes in liver tumor size and metabolic activity.
- Designer T cell distribution following infusion [ Time Frame: 1 month ]Using liver tumor biopsy specimens and blood collection, we will determine the extent to which infused T cells enter the liver tumors in addition to circulation in the extrahepatic space.
- Designer T cell survival and phenotype following infusion [ Time Frame: 1 month ]Using tissue obtained from biopsies in addition to blood samples, the duration of T cell persistence will be assessed, in addition to cell surface markers.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01373047
|United States, Rhode Island|
|Roger Williams Medical Center|
|Providence, Rhode Island, United States, 02908|
|Principal Investigator:||Steven C Katz, MD||Roger Williams Medical Center|