Sponsored by Baylor College of Medicine

Phase	Quota	Distance
Phase 1		Near

Patients have nasopharyngeal carcinoma (NPC). This study is a gene transfer research study using special immune cells. Most patients with NPC show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, suggesting that it may play a role in causing the disease. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called T cells, that have been trained to recognize and kill special parts of EBV infected cells can survive in patient's blood and affect the tumor. We already have given EBV-specific cytotoxic T cells to 30 patients with active NPC and have seen anti-tumor activity in 14 of 30 patients. We are now trying to find out if we can improve this treatment. First, we want to give T cells where more of the cells recognize at least two of the four EBV proteins expressed on NPC cells. We call these cells NPC-specific cytotoxic T cells. Second, we found that T cells work better if we add a receptor to the T cells called DNR (Dominant Negative Receptor). DNR makes T cells resistant to TGFbeta, a factor secreted by cancer cells that helps them escape being killed by the immune system. In this study we will therefore place the DNR gene into NPC-specific T cells (DNR.NPC-specific T cells).

Study Start Date: February 2015

Estimated Completion Date: February 2033

Specialties: Oncology: Head and Neck Otolaryngology: Head and Neck,Larynx/Trachea/Airway,Nose

Interventions

• Genetic: DNR.NPC-specific T cells

Inclusion criteria

At time of Procurement:

• Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease
• EBV positive tumor
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

At time of Treatment:

• Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease
• EBV positive tumor
• Patients with life expectancy greater than or equal to 6 weeks
• Bilirubin less than or equal to 3x upper limit of normal
• AST less than or equal to 5x upper limit of normal
• Hgb > 8.0g/dl (can be transfused)
• Creatinine less than or equal to 2x upper limit of normal for age
• Pulse oximetry of > 90% on room air
• Off investigational therapy for 4 weeks prior to study entry
• Karnofsky or Lansky score of greater than or equal to 50%
• Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion criteria

At time of Procurement:

• Known HIV positivity

At time of Treatment:

• Pregnant or lactating
• Severe intercurrent infection

Study Locations And Contact Information

• Houston Methodist Hospital, Houston Texas
  Contact: Stephen Gottschalk MD 832-824-4179 smgottsc@txch.org
• Texas Childrens Hospital, Houston Texas
  Contact: Stephen Gottschalk MD 832-824-4179 smgottsc@txch.org