Prevention and Treatment of Epstein-Barr Virus (EBV) Lymphoma Following a Solid Organ Transplant Using EBV Specific Cytotoxic T Lymphocytes (CTLs).

NCT ID: NCT00058604

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-01-31
• Study Completion Date: 2008-12-31

Brief Summary

Patients who may have been infected with EBV (Epstein-Barr Virus) before or after the time of their transplant have a higher risk of developing Lymphoproliferative Disease (LPD) or may already have a form of this disease.

This research study uses Epstein Barr virus (EBV) specific cytotoxic T lymphocytes (CTLs). These cells have been trained to attack and kill (cytotoxic) EB virus infected cells.

We make these cells from the patients blood by first growing an EBV infected B cell line by infecting the blood with an EBV virus called B-95. We then treat these EBV infected B cells with radiation so they cannot grow and use them to stimulate T cells. This stimulation will train the T cells to kill EBV infected cells. We will then test the T cells to make sure they kill the EBV infected cells.

The purpose of this study is to find the largest safe dose of EBV specific CTLs, to learn what the side effects are, and to see whether this therapy might help prevent or cure EBV related cancers in solid organ transplant patients

Detailed Description

Participation in this study will be for one year. Patients will receive this treatment either while in hospital or in the outpatient clinic. Each patient 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 unacceptable side effects are seen.

First, patients will be given Tylenol (for any aches/pains) and Benadryl (for any minor allergic reactions such as itching/rash). This is called premedication. Next, the T cells will be injected into the patients' vein (intravenously) over approximately 10 minutes. Patients will be closely watched during this time to make sure they do not experience any bad effects such as an allergic reaction. If the patient does not respond to the T cells or if during follow-up examinations evidence of relapse is shown, the patient may receive another (higher) dose of T cells approximately six weeks after their first injection. Patients may decide NOT to continue to receive this therapy (receive further injections), however, the follow-up period will still be for one year.

Each patient will be seen every two weeks in the clinic or contacted every two weeks by the research nurse or other member of the research team, for six weeks after the injection(s). They will then be seen or contacted monthly for 3 months and then once every three months for one year and again if relapse occurs or is suspected.

To learn more about the way the T cells are working and how long they last in the body, 40 mls (8 teaspoonfuls) of blood will be taken once before the injection of T-cells, every two weeks for 6 weeks after the injection, monthly for 3 months and then every 3 months for 1 year. This amount of blood will be less for small patients. We will also take another blood sample from the patient if relapse is suspected. Each patient will need to have a physical examination by their physician to check on their progress.

Additionally, before the injection of T-cells, once every two weeks after the injection for 6 weeks and once every month for 3 months and then once every 3 months for one year and again if relapse occurs or is suspected we will obtain a blood sample from the patient to evaluate for transplant rejection. The amount of blood that we will take will be 3-5 mls (1/2 to 1 teaspoon). If the patient has received a heart transplant they will also be asked to have other tests such as an ultrasound or tomography (similar to an x-ray) done to help with this evaluation.

Conditions

Epstein-Barr Virus Infections; Lymphoproliferative Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Each patient will receive a Biological/Vaccine Intravenous injection of EBV specific CTLs

Group Type: EXPERIMENTAL

Intravenous injection of EBV specific CTLs

Intervention Type: BIOLOGICAL

Each patient will receive injections of 2x10e7 , 5x10e7 , or 10e8 CTLs/m2 via IV injection. 6 weeks = 1 course

Interventions

Intravenous injection of EBV specific CTLs

Each patient will receive injections of 2x10e7 , 5x10e7 , or 10e8 CTLs/m2 via IV injection. 6 weeks = 1 course

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients falling into one of the following categories:

• Organ transplant recipients at high risk of developing LPD:
• EBV seronegative recipients
• Organ transplant recipients receiving OKT3 for immunosuppression
• Organ transplant recipients with evidence of LPD
• Organ transplant recipients with EBV DNA level >1,000 copies
• Age <70 yrs old
• Signed informed consent obtained from patient/guardian
• CTLs available
• Performance status; ECOG £ 2
• Creatinine < 3X normal
• Bilirubin < 5X normal
• AST < 5X normal
• Has not received any other investigational cellular therapies within the past 30 days.

Exclusion Criteria

• Patients with a severe intercurrent infection
• Patients with life expectancy of less than 6 weeks
• Patients receiving supplemental oxygen.

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Methodist Hospital Research Institute

OTHER

Sponsor Role: collaborator

Center for Cell and Gene Therapy, Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Helen Heslop

Professor/Director Center for Cell and Gene Therapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Helen Heslop, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Texas Children's Hospital

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

Countries

United States

Other Identifiers

Euclid

Identifier Type: -

Identifier Source: secondary_id

H9454

Identifier Type: -

Identifier Source: org_study_id

NCT00607698

Identifier Type: -

Identifier Source: nct_alias