LMP2a-Specific Cytotoxic T-Lymphocytes, Lymphoma (ACDAL)

Summary

Patients have a type of cancer called Hodgkin's lymphoma or non-Hodgkin's lymphoma, which has come back or not gone away or is at high risk for coming back after treatment, including the best treatment investigators know for this disease. Investigators are asking the patient to volunteer to be in a research study using a new experimental therapy consisting of special immune system cells called LMP2 specific cytotoxic T lymphocytes in combination with a special protein called a monoclonal antibody.

Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of the lymphoma. EBV is found in the cancer cells of up to half the patients with lymphoma, suggesting that 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 destruction. Investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor.

The investigators have used this sort of therapy 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 the tumor cells have 9 proteins made by EBV on their surface. They grew T cells in the laboratory that recognized all 9 proteins and were able to prevent and treat post transplant lymphoma. However in Hodgkin disease and non-Hodgkin Lymphoma the tumor cells only express 2 EBV proteins. In a previous study investigators made T cells that recognized all 9 proteins and gave them to patients with Hodgkin disease. Some patients had a partial response to this therapy but no patients had a complete response. Investigators think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. They are now trying to find out if they can improve this treatment by growing T cells that only recognize one of the proteins expressed on Lymphoma cells called LMP-2. These special T cells are called LMP-2 specific cytotoxic T-lymphocytes (CTLs).

In this study investigators also are trying to see if they can improve these results by treating patients first with a special protein called an antibody and then giving the EBV specific T cells. The reason for doing this is that EBV specific T cells have worked very well in bone marrow transplant patients to prevent and treat EBV cancers. These patients have very few of their own immune cells when they are given the trained T cells and therefore there is a lot of space for the trained cells to grow. Investigators hope that they can improve the effect of the trained T cells in Hodgkin disease and non-Hodgkin Lymphoma patients by first temporarily removing the patient's own T cells before giving the trained cells.

Conditions

• Lymphoma

Interventions

BIOLOGICAL

CD45 antibodies

The antibody solution is administered by a syringe pump in incremental doses, 0.2-0.8 mg in the first hour and up to 10 mg/hr thereafter, for a maximum infusion time of 8 hrs.

BIOLOGICAL

EBV specific T cells

The following dose levels will be evaluated: Each patient will receive 1 injection, according to the following dosing schedules: 2 x 10e7 cells/m2 5 x 10e7 cells/m2 1 x 10e8 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

2003-10-31

Primary Completion

2006-02-28

Completion

2008-01-31

Countries

• United States

Study Locations