Cytotoxic T Cells to Treat Relapsed EBV-positive Lymphoma

Summary

In this study, investigators are trying to see if LMP specific cytotoxic T lymphocytes (CTLs) will prevent or treat disease called Epstein Barr Virus (EBV) Disorder including either Hodgkin Lymphoma or non-Hodgkin Lymphoma or Lymphoepithelioma or severe chronic active EBV infection syndrome (SCAEBV) or Leiomyosarcoma which has come back or has not gone away after treatment, including the best treatment. Investigators are using special immune system cells called third party LMP specific cytotoxic T lymphocytes (CTLs), a new experimental therapy.

Some patients with Lymphoma or SCAEBV or Leiomyosarcoma 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 up to half the patients with Hodgkin's and non-Hodgkin Lymphoma, suggesting that it may play a role in causing Lymphoma. The cancer cells (in lymphoma) and some B cells (in SCAEBV) infected by EBV are able to hide from the body's immune system and escape destruction. The investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in patient's blood and affect the tumor or infection.

Investigators used this sort of therapy to treat a different type of cancer that occurs after bone marrow or 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 successfully prevent and treat post transplant lymphoma. However in Hodgkin Lymphoma, the tumor cells and B cells only express 2 EBV proteins. In a previous study they made T cells that recognized all 9 proteins and gave them to patients with Hodgkin Lymphoma. Some patients had a partial response to this therapy but no patients had a complete response. They think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. In this present study the investigators are trying to find out if the investigators can improve this treatment by growing T cells that recognize proteins expressed on EBV infected Lymphoma cells and B cells called LMP-1 and LMP2. These special T cells are called third party LMP 1/2 -specific cytotoxic T-lymphocytes (CTLs). These LMP-specific cytotoxic

T cells are an investigational product not approved by the Food and Drug Administration.

Conditions

• Hodgkin Disease
• Non Hodgkin Lymphoma
• Lymphoepithelioma
• Severe Chronic Active EBV Infection Syndrome (SCAEBV)
• Leiomyosarcoma

Interventions

DRUG

LMP1/2 CTLs (Group A)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One: Day 0: 1 x 107 cells/m2 Day 14: 1 x 107 cells/m2 Dose Level Two: Day 0: 2 x 107 cells/m2 Day 14: 2 x 107 cells/m2 Dose Level Three: Day 0: 5 x 107 cells/m2 Day 14: 5 x 107 cells/m2

DRUG

LMP1/2 CTLs (Group B)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One: Day 0: 1 x 107 cells/m2 Day 14: 1 x 107 cells/m2 Dose Level Two: Day 0: 2 x 107 cells/m2 Day 14: 2 x 107 cells/m2 Dose Level Three: Day 0: 5 x 107 cells/m2 Day 14: 5 x 107 cells/m2

Sponsors & Collaborators

• Catherine Bollard

  lead OTHER

Principal Investigators

• Catherine Bollard, MD · CNMC

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-11-30

Primary Completion

2017-11-19

Completion

2019-10-15

Countries

• United States

Study Locations