TGF-beta Resistant Cytotoxic T-lymphocytes in Treatment of EBV-positive Nasopharyngeal Carcinoma / RESIST-NPC

Summary

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.

Conditions

• EBV-positive Nasopharyngeal Carcinoma

Interventions

BIOLOGICAL

DNR.NPC-specific T cells

Each patient will receive 2 infusions, 14 days apart, according to the following dosing schedule: Dose Level 1: Day 0: 2 x 10\^7 cells/m\^2 Day 14: 2 x 10\^7 cells/m\^2 The doses are calculated according to the total T cell number.

BIOLOGICAL

DNR.NPC-specific T cells + cyclophosphamide + fludarabine

Patients will receive cyclophosphamide and fludarabine for 3 days before receiving the DNR.NPC-specific T cells. Each patient will receive infusions according to the following dosing schedule: Dose Level 2: Cy/Flu on Days -4 to -2 and then 4 x 10\^7 cells/m\^2 on Day 0, Day 1 or Day 2 Dose Level 3: Cy/Flu on Days -4 to -2 and then 1 x 10\^8 cells/m\^2 on Day 0, Day 1, or Day 2

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Helen Heslop, MD · Baylor College of Medicine/Texas Children's Hospital /Houston Methodist Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-02-28

Primary Completion

2017-03-31

Completion

2033-02-28

Countries

• United States

Study Locations