Autologous/Allogeneic TGFbeta-resistant LMP-specific CTL, Lymphoma (TGF-beta)

Summary

Patients have a type of lymph gland cancer called HD, NHL or lymphoepithelioma (these 3 diseases will be referred to as "Lymphoma"). The lymphoma has come back or has not gone away after treatment. This is a research study using special immune system cells called TGFb-resistant LMP-specific cytotoxic T lymphocytes (DNR-CTL), a new experimental therapy.

Some patients with Lymphoma show signs of infection with the Epstein Barr virus (EBV) before or at the time of their Lymphoma diagnosis. EBV is found in the cancer cells of up to 1/2 the patients with Lymphoma, suggesting it may play a role in causing Lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed by releasing a substance called Transforming Growth Factor-beta (TGFb). The investigators want to see if special white blood cells (called T cells) that have been given a gene that they hope will let them survive against TGFb and that have been trained to kill EBV infected cells can also survive in the blood and kill the tumor.

Investigators have used this sort of therapy with specially trained T cells to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post transplant lymphoma. In this type of cancer they were able to successfully prevent and treat post transplant lymphoma. However when they used a similar approach in HD some patients had a partial response to this therapy, but no patients had a complete response. In a follow-up study they tried to find out if they could improve this treatment by growing T cells that recognize 2 of the proteins expressed on Lymphoma cells called LMP-1 and LMP2a. These special T cells were called LMP-specific cytotoxic T-lymphocytes (CTLs). Although some patients had tumor responses, CTL therapy alone did not cure those who had a lot of disease. Investigators think that a reason for this is that the tumor cells are releasing TGFb. For this reason, they want to find out if they can make the CTL resistant to TGFb by putting in a new gene called TGFb resistance gene. Investigators hope that this will improve this treatment for relapsed lymphoma. These TGFb-resistant LMP-specific CTLs are an investigational product not approved by FDA.

The purpose of this study is to find the largest safe dose of TGFb resistant LMP-specific CTLs, to learn what the side effects are and to see whether this therapy might help patients with Lymphoma.

Conditions

• Lymphoma
• Hodgkin's Disease
• Relapse
• Lymphoma, Non-Hodgkin

Interventions

BIOLOGICAL

TGFbeta resistant LMP-specific CTLs

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Group One: Day 0 2 x 10\^7 cells/m2 Day 14 2 x 10\^7 cells/m2 Group Two: Day 0 6 x 10\^7 cells/m2 Day 14 6 x 10\^7 cells/m2 Group Three: Day 0 1.5 x 10\^8 cells/m2 Day 14 1.5 x 10\^8 cells/m2

Sponsors & Collaborators

• The Methodist Hospital Research Institute

  collaborator OTHER

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

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Helen E Heslop, MD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-04-30

Primary Completion

2013-09-30

Completion

2031-07-31

Countries

• United States

Study Locations