Her2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma
Patients have a type of cancer called sarcoma. The sarcoma has come back after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in 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 disease: antibodies and T cells. We hope that both will work better together. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing or exerting their toxic effects. 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.
We have found from previous research that we can put a new gene into T cells that will make them recognize cancer cells and kill them. We now want to see if we can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that we will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition it contains CD28, which stimulated T cells and make them last longer.
The purpose of this study is to find the largest safe dose of chimeric T cells, to learn what the side effects are, and to see whether this therapy might help patients with sarcoma.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Administration of Her2 Chimeric Antigen Receptor Expressing T Cells for Subjects With Advanced Sarcoma (HEROS)|
- Number of patients with dose limiting toxicity after one injection of HER2-specific T cells [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]To determine the safety of one intravenous injection of autologous T cells expressing HER2-specific chimeric antigen receptor (CAR) in patients with advanced HER2-positive sarcoma.
- Frequency of HER2-specific T cells pre and post injection [ Time Frame: 15 years ] [ Designated as safety issue: No ]To assess the in vivo persistence of infused T cells using immunoassays and transgene detection
- Change in tumor size from pre to post injection [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]To assess the anti-tumor effects of the infused HER2-specific T cells
|Study Start Date:||July 2009|
|Estimated Study Completion Date:||July 2030|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Experimental: Autologous HER2-specific T cells
Dose Level 1: 1x10^4 cells/m2
Dose Level 2: 3x10^4 cells/m2
Dose Level 3: 1x10^5 cells/m2 (NOT BEING USED)
Dose Level 4: 3x10^5 cells/m2 (NOT BEING USED)
Dose Level 5: 1x10^6 cells/m2
Dose Level 6: 3x10^6 cells/m2
Dose Level 7: 1x10^7 cells/m2
Dose Level 8: 3x10^7 cells/m2
Dose Level 9: 1x10^8 cells/m2
Genetic: Autologous HER2-specific T cells
Each patient will receive one intravenous injection of autologous HER2-specific T cells at one of the dose levels.
If the patient has stable disease or a reduction in the size of the tumor they can receive up to 6 additional doses of T cells.
Because the cells have a new gene in them the patient will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.
When the patient is enrolled on this study, they will be assigned a dose of HER2-CD28 T cells.
The patient will be given an injection of cells into the vein through an IV line at the assigned dose. 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.
Each patient will be followed for 6 weeks after the T-cell infusion for evaluation of toxicity. They will have standard tests and procedures as well as research blood draws.
If the patient has stable disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging studies after the T-cell infusion, they can receive additional doses of the T cells at 6 to 12 weeks intervals.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00902044
|Contact: Nabil M Ahmed, MDfirstname.lastname@example.org|
|Contact: Catherine Pereraemail@example.com|
|United States, Texas|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Nabil M Ahmed, MD 832-824-4611 firstname.lastname@example.org|
|Contact: Stephen Gottschalk, MD 832-824-4179 email@example.com|
|Houston Methodist Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Nabil M Ahmed, MD 832-824-4611 firstname.lastname@example.org|
|Contact: Stephen S Gottschalk 832-824-4719 email@example.com|
|Principal Investigator:||Nabil M Ahmed, MD||Baylor College of Medicine/Texas Children's Hospital|