LMP-specific T-cells for Patients With Relapsed EBV-positive Lymphoma

Summary

This protocol is broken up into 2 portions to determine the maximum tolerated dose for treating patients with a type of lymph gland disease.

The 1st portion, called ALASCER are for people with a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma or Lymphoepithelioma which has returned or may return or has not gone away after treatment, including the best treatment we know for Lymphoma. While the 2nd portion (ALCI) also includes Lymphoepithelioma, severe chronic active EBV (SCAEBC), and leiomyosarcoma.

Some patients with Lymphoma 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. Investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in your 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 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. The investigators 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 disease and non-Hodgkin Lymphoma and SCAEBV, the tumor cells and B cells only express 2 EBV proteins. In a previous study we 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. In this present study we are trying to find out if we can improve this treatment by growing T cells that only recognize one of the proteins expressed on infected EBV Lymphoma cells called LMP-2a, and B cells called LMP1 and LMP2. These special T cells are called LMP specific cytotoxic T-lymphocytes (CTLs).

The purpose of the study is to find the largest safe dose of LMP specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease, non-Hodgkin Lymphoma, Lymphoepithelioma, SCAEBV or leiomyosarcoma.

Conditions

• Hodgkin Disease
• Non Hodgkin Lymphoma
• Lymphoepithelioma
• Leiomyosarcoma

Interventions

BIOLOGICAL

LMP1/2 CTLs (ALCI - Group A)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2 x 10\^7 cells/m2; Day 14: 2 x 10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2

BIOLOGICAL

LMP1/2 CTLs (ALCI - Group B)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2

BIOLOGICAL

LMP1/2 CTLs (ALCI - Group C)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2

BIOLOGICAL

LMP2 CTLs (ALSCER - Group A)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2 x 10\^7 cells/m2; Day 14: 2 x 10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2

BIOLOGICAL

LMP2 CTLs (ALSCER - Group B)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2

BIOLOGICAL

LMP2 CTLs (ALSCER - Group C)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2 Dose Level Two Day 0: 2x10\^7 cells/m2; Day 14: 1x10\^8 cells/m2 Dose Level Three Day 0: 1x10\^8 cells/m2; Day 14: 2x10\^8 cells/m2

BIOLOGICAL

LMP1/2 CTLs (ALCI - Expansion - Group A)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2 x 10\^7 cells/m2; Day 14: 2 x 10\^7 cells/m2

BIOLOGICAL

LMP1/2 CTLs (ALCI - Expansion Group B)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 cells/m2

BIOLOGICAL

LMP1/2 CTLs (ALCI - Expansion Group C)

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Dose Level One Day 0: 2x10\^7 cells/m2; Day 14: 2x10\^7 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 · Center for Cell and Gene Therapy, Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2003-09-30

Primary Completion

2014-04-30

Completion

2020-04-30

FDA Drug

Yes

Countries

• United States

Study Locations