Her2 and TGFBeta CTLs in Treatment of Her2 Positive Malignancy (HERCREEM)
Patients have advanced stage cancer. This study is a gene transfer research study using special immune cells.
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Investigators hope that both will work better together. Antibodies are proteins that protect the body from diseases caused from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients.
T lymphocytes can kill tumor cells but there are normally not enough of them or they are not able to kill all the tumor cells. We have done research in which we have grown "extra" T lymphocytes. We have added genes to those T lymphocytes to help them to recognize tumor cells. Although the results have been promising, we are still doing more research in this area.
Antibodies usually circulate in blood and are secreted by other cells of the immune system in response to the presence of germs or abnormal cells in the body. The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to HER2-positive cancer cells because of a substance on the outside of these cells called HER2.
|HER2 Positive Malignancies||Biological: TGFBeta resistant HER2/EBV-CTLs||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Administration of Her2 Chimeric Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Malignancy (HERCREEM)|
- Determine safety of one IV injection of autologous TGFBeta-resistant CTLs directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2-positive cancers. [ Time Frame: 6 weeks ]
- To compare the survival and the immune function of the TGFBeta-resistant and non resistant components of the infused CAR-CTL. [ Time Frame: 15 years ]
- To assess the anti-tumor effects of the infused CAR-CTL. [ Time Frame: 15 years ]
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||June 2030|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Experimental: TGFBeta resistant HER2/EBV-CTLs
The following dose levels will be evaluated:
Dose Level 1: 1 x 10^4 cells/m^2
Dose Level 2: 3 x 10^4 cells/m^2
Dose Level 5: 1 x 10^6 cells/m^2
Dose Level 6: 3 x 10^6 cells/m^2
Dose Level 7: 1 x 10^7 cells/m^2
Dose Level 8: 3 x 10^7 cells/m^2
Dose Level 9:1 x 10^8 cells/m^2
Biological: TGFBeta resistant HER2/EBV-CTLs
Each patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs. Each pt will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT).
Patients may receive up to six additional doses of the T cells at 6 to 12 weeks intervals.
Other Name: HER2 Chimeric Receptor & TGFbeta Dominant Negative Receptor (DNR) Expressing EBV specific lymphocytes
The patient will give blood to grow T cells on either one to two separate occasions. Then, the EBV-specific T cells will be made. These cells will be grown and frozen. To get the HER2 antibody (and the CD28) and the DNR to attach to the surface of the EBV-T cells, the antibody gene and the DNR gene will be inserted into the EBV-T cell. This is done with two viruses called retroviruses that have been made for this study. One will carry the antibody gene into the T cell and the other the DNR gene.
When the patient is enrolled on the study, they will be assigned to a dose of HER2-DNR EBV-T cells. The subject will be given one dose of cells into the vein through an IV line. The injection will take between 1 and 10 minutes. The patient will be followed in the clinic after the injection for 1 to 4 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00889954
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Stepehen Gottschalk, MD||Baylor College of Medicine/Texas Children's Hospital|