Autologous T Cells Expressing Enhanced TCRs Specific for MAGEA3/A6/B18 or NYESO-1/LAGE in Patients With Ovarian Cancer
This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A1 tissue-type marker, T cells would be engineered to recognize a substance on the ovarian cancer cells called "MAGE A3/A6/B18". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY ESO 1/LAGE". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/IIa, Open Label, Dual Cohort, Triple Center Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for MAGE-A3/A6/B18 or NYESO-1/LAGE in Patients With Recurrent or Treatment Refractory Ovarian Cancer|
- NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3 [ Time Frame: Month: 9 ] [ Designated as safety issue: Yes ]This will evaluate safety of autologous genetically modified T cells transduced to express the high affinity MAGE-A3a3a TCR in HLA-A101 subjects, and the high affinity NY-ESO-1c259 TCR in HLA-A201 subjects.
- Tumor Measurements [ Time Frame: Month 9 ] [ Designated as safety issue: No ]To measure the effect of MAGE-A3a3a-T and NY-ESO-1c259-T on tumor as measured by Immune-related Response Criteria and progression free survival
|Study Start Date:||February 2012|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
Subjects who are HLA A101 positive and their tumor expresses MAGE-A3/MAGE-A6/MAGE- B18 positive.
Biological: T cells
Subjects who are HLA A101 positive and their tumor expresses MAGE-A3/MAGE-A6/MAGE- B18 positive will undergo apheresis, T cell infusion and frequent follow up for 9 months. Subjects will then undergo long term follow up for up to 15 years.
Experimental: Cohort 2
Subjects who are HLA A201 positive and their tumor expresses NY-ESO-1 and/or LAGE positive.
Biological: T cells
Subjects who are HLA A201 positive and their tumor expresses NY-ESO-1 and/or LAGE positive will undergo apheresis, T cell infusion and frequent follow up for 9 months. Subjects will then undergo long term follow up for up to 15 years.
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Study Chair:||Kunle Odunsi, MD, PhD||Roswell Park Cancer Institute|