TGF-beta Resistant Cytotoxic T-lymphocytes for Nasopharyngeal Cancer

Recruiting in Palo Alto (17 mi)

Overseen byHelen Heslop, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Baylor College of Medicine

No Placebo Group

Trial Summary

What is the purpose of this trial?

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). In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of patient's lymphocytes first should allow the T cells we infuse to expand and stay longer in their body, and potentially kill cancer cells more effectively. The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used for lymphodepletion in immunotherapy clinical trials.

Research Team

Helen Heslop, MD

Principal Investigator

Baylor College of Medicine/Texas Children's Hospital /Houston Methodist Hospital

Eligibility Criteria

This trial is for people with nasopharyngeal carcinoma, a type of cancer linked to the Epstein-Barr virus. Participants must have a certain level of white blood cells, kidney function within specific limits, and not be pregnant or HIV positive. They should expect to live at least six weeks and agree to use effective birth control during and after the study.

Inclusion Criteria

The patient must meet the following eligibility criteria to be included for 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, ANC>750/microliter, Platelets > 50,000/microliter, Hgb ≥ 7.0g/dl (can be transfused), Creatinine less than or equal to 2x upper limit of normal for age, Creatinine clearance (as estimated by Cockcroft Gault or Schwartz) greater than or equal to 60 ml/min, 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.

I have nasopharyngeal carcinoma that has returned or didn't respond to treatment, and it's EBV positive. I've signed the informed consent.

Exclusion Criteria

I am not pregnant, breastfeeding, or have a severe infection.

At time of Procurement: Known HIV positivity

Treatment Details

Interventions

Cyclophosphamide and Fludarabine (Chemotherapy)
DNR.NPC-specific T cells (CAR T-cell Therapy)
NPC-specific cytotoxic T cells (CAR T-cell Therapy)

Trial OverviewThe trial tests genetically modified T cells designed to fight cancer by targeting EBV-infected cells in patients with nasopharyngeal carcinoma. Some participants will receive these T cells alone, while others will also get chemotherapy drugs cyclophosphamide and fludarabine beforehand to potentially enhance results.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: DNR.NPC-specific T cells or DNR.NPC-specific T cells + c/fExperimental Treatment2 Interventions

DNR.NPC-specific T cells or DNR.NPC-specific T cells + c/f