iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma/VEGAS
|ClinicalTrials.gov Identifier: NCT01953900|
Recruitment Status : Active, not recruiting
First Posted : October 1, 2013
Last Update Posted : August 16, 2017
PLEASE NOTE - THIS STUDY IS CURRENTLY ONLY RECRUITING PARTICIPANTS WITH OSTEOSARCOMA.
The purpose of this study is to find the largest safe dose of GD2-T cells (also called iC9-GD2-CAR-VZV-CTLs), and additionally to evaluate if a VZV vaccine can improve the expansion and persistence of infused T cells, to learn what the side effects are, and to see whether this therapy might help patients with advanced sarcomas. Because there is no standard treatment for recurrent/refractory sarcomas 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 cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients.
Investigators have found from previous research that a new gene can be put into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if a new gene can be put in these cells that will let the T cells recognize and kill sarcoma cells. The new gene is called a chimeric antigen receptor (CAR) and consists of an antibody called 14g2a that recognizes GD2, a protein that is found on sarcoma cells (GD2-CAR). In addition, it contains parts of the CD28 and OX40 genes which can stimulate T cells to make them live longer.
Investigators have found that CAR-T cells can kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. T cells that recognize the virus that causes chicken pox, varicella zoster virus (VZV), remain in the bloodstream for many years especially if they are stimulated or boosted by the VZV vaccine. Investigators will therefore insert the GD2-CAR gene into T cells that recognize VZV. These cells are called iC9-GD2-CAR-VZV-specific T cells but are referred to as GD2-T cells for simplicity.
|Condition or disease||Intervention/treatment||Phase|
|Sarcomas||Genetic: GD2 T cells Biological: VZV vaccine||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Vaccination to Enhance the Anti-Tumor Activity of GD2 Chimeric Antigen Receptor-Expressing, VZV-Specific T Cells in Subjects With Advanced Sarcomas (VEGAS)|
|Study Start Date :||April 2014|
|Estimated Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||April 2033|
|Experimental: GD2 T cells plus VZV vaccine||
Genetic: GD2 T cells
On dose levels 1 and 2 each patient receives one injection of GD2 T cells followed by VZV vaccine injection 42 days later.
Dose levels 1 and 2 are:
Dose Level 1: 1x10^6 cells/m^2
Dose Level 2: 1x10^7 cells/m^2
The next dose levels to be studied following Dose level 2 are Dose levels 7 and 8 where subjects will receive the VZV vaccine followed by a single infusion of iC9-GD2-CAR-VZV-CTLs within 48 hours after VZV vaccine:
Dose Level 7: 1 x 10^7 cells/m2
Dose Level 8: 1 x 10^8 cells/m^2
The previously planned dose levels 3-6 will not be studied.
Other Name: iC9-GD2-CAR-VZV-CTLBiological: VZV vaccine
Subjects will receive a VZV vaccine with CTL infusion within 48 hours after the vaccine.
Other Name: zostavax
- Number of subjects with a dose limiting toxicity [ Time Frame: 6-weeks ]The primary objective is to evaluate the safety and feasibility of intravenous injections of autologous iC9-GD2-CAR-VZV-CTLs in combination with VZV vaccination in patients with advanced GD2-positive sarcomas.
- Number of patients with a response to the T cells [ Time Frame: 14 weeks ]
To assess the anti-tumor effects of the infused GD2-specific T cells
Evaluations of tumor size will be performed within 4 weeks of beginning treatment and 6 weeks (before the vaccine) and 12 to 14 weeks after the iC9-GD2-CAR-VZV-CTL injection. All patients who receive the first infusion will be evaluable for response.
- Amount of T cells in the blood after the infusions [ Time Frame: 15 years ]
To assess the effects of VZV vaccination on the in vivo expansion and persistence of transgenic VZV-specific T cells
To assess the in vivo persistence of infused T cells using immunoassays and transgene detection
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01953900
|United States, Texas|
|Houston Methodist Hospital|
|Houston, Texas, United States, 77030|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Lisa L Wang, MD||Baylor College of Medicine|