Safety Study of EBV Specific Cytotoxic T-Cells to Treat Relapsed EBV-Positive Lymphoma,

Condition(s) targeted: EBV Positive Hodgkins Disease; EBV Positive Non-Hodgkins Lymphoma; EBV Positive Plasma Cell Neoplasm

Intervention: Injection of EBV Specific Cytotoxic T-Lymphocytes (Procedure)

Phase: Phase 1

Status: Recruiting

Sponsored by: Baylor College of Medicine

Official(s) and/or principal investigator(s):
Helen Heslop, M.D., Study Chair, Affiliation: Baylor College of Medicine

Overall contact:
Helen Heslop, MD, Phone: 832-824-4662

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 Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. We want to see if we can grow special white blood cells, called T cells, that have been trained to kill EBV infected cells and then give them back to the patient. To find out how long these cells last we may put a marker gene into them so we can track them. Gene marking is optional in this study. Eligible patients can participate without the gene marking if they choose.

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

Official title: The Administration of Neomycin Resistance Gene Marked EBV Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma.

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

To determine the safety of two IV injections of auto EBV specific CTLs in patients with relapsed Hodgkin disease or Non-Hodgkin Lymphoma. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector.

To determine the feasibility of generating EBV specific cytotoxic T cell lines from patients with active EBV positive Lymphoma including Hodgkin Disease (HD) or Non-Hodgkin Lymphoma (NHL).

To determine the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.

To obtain preliminary information on the safety and response to an extended dosage regimen.

Detailed description: We will take 60-70 ml (12 teaspoonfuls) of blood from the patient to make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95. We will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. We will then test the T cells to make sure that they kill the EBV infected cells and not normal cells and freeze them.

Patients will be entered into one of three different dosing schedules being evaluated. Three to six patients will be evaluated on each dosing schedule. Escalation will continue until irreversible or life threatening side effects considered to be related to the T cells are seen.

For patients who agree to gene marking (this is optional), we will mark these cells with a special bacterial marker gene. We will use a mouse virus (retrovirus) that has been changed to stop it from causing infection. The marker, a gene called Neo, is put inside this special virus.

The cells will be injected into the patients' vein over 10 minutes, after pretreatment with Tylenol and Benadryl. Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration. A total of two doses will be given two weeks apart. All of the treatments will be given at Texas Children's Hospital or The Methodist Hospital.

Patients will be followed in the clinic after the injections. At each visit about 10ml (2 teaspoonfuls) of blood will be taken every other week for 6 weeks after the injection and then every 3 months for 1 year to monitor the patients' blood chemistry and hematology.

For patients who agreed to gene marking, an extra 8 teaspoons (40 mls) of blood will be taken before each infusion, 24 hours after each infusion, 3-4 days after each infusion and at 1, 2, 4, and 6 weeks post infusion and then at 3, 6, 9 and 12 months post infusion) then once every 6 months for the first 5 years and then yearly thereafter for the next 10 years. We will use this blood to test for the frequency and activity of EBV specific T cells. That is, to learn more about the way the T cells are working and how long they last in the body.

We will also use this blood to see if there are any long term side effects of gene transfer. Patients who received cells that have a marker gene will need to be followed (seen in clinic or contacted by a research nurse) at least every six months for the next five years and then yearly thereafter for the next ten years so we can see if there are any long term side effects of the gene transfer.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Any patient with EBV positive Hodgkin disease or non-Hodgkin Lymphoma, in second

relapse regardless of age or sex, in first relapse or with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e. g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e. g. a Richters transformation of CLL.

- Patients with a life expectancy >6 weeks.

- Patients with a Karnofsky score of > 50.

- No severe intercurrent infection.

- Patient, parent/guardian able to give informed consent.

- Patients with bilirubin <2x normal, SGOT <3x normal, and Hgb >8. 0.

- Patients with a creatinine <2x normal for age.

- Patients should have been off other investigational therapy for one month prior to

entry in this study.

Exclusion Criteria

- Patients with an EBV positive NHL secondary to an acquired or congenital

immunodeficiency.

- Patients who are HIV positive.

- Patients with a life expectancy of <6 weeks.

- Patients with a Karnofsky score of < 50.

- Patient, parent/guardian unable to give informed consent.

- Patients with a bilirubin >2x normal. SGOT >3x normal.

- Patients with a creatinine >2x normal for age

- Due to unknown effects of this therapy on a fetus, pregnant women are excluded from

this research. The male partner should use a condom.

Helen Heslop, MD, Phone: 832-824-4662

Texas Children's Hospital, Houston, Texas 77030, United States; Recruiting
Helen E Heslop, MD, Phone: 832-824-4662, Email: hheslop@bcm.tmc.edu
Helen E Heslop, MD, Principal Investigator

The Methodist Hospital, Houston, Texas 77030, United States; Completed

Starting date: January 1996
Ending date: December 2014
Last updated: July 30, 2009