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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00058604
Recruitment Status : Completed
First Posted : April 9, 2003
Last Update Posted : April 10, 2009
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by:
Baylor College of Medicine

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

Condition or disease Intervention/treatment Phase
Epstein-Barr Virus Infections Lymphoproliferative Disorders Biological: Intravenous injection of EBV specific CTLs Phase 1

Expanded Access : Baylor College of Medicine has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous EBV Specific CTLs for Prophylaxis and Therapy of EBV Lymphoma Post Solid Organ Transplant
Study Start Date : January 2001
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Intervention Details:
  • Biological: 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

Primary Outcome Measures :
  1. Generate autologous, EBV-specific, cytotoxic T cell lines (CTLs) from individuals receiving or having received a solid organ transplant (SOT). [ Time Frame: pre-treatment ]
  2. Administer autologous, EBV-specific CTLs to patients, to determine the safety of intravenous injections in these individuals [ Time Frame: 1 year ]
  3. Evaluate the antiviral and immunological efficacy of the infused CTLs [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00058604

United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
The Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Principal Investigator: Helen Heslop, MD Baylor College of Medicine

Responsible Party: Helen Heslop, Baylor College of Medicine Identifier: NCT00058604     History of Changes
Obsolete Identifiers: NCT00607698
Other Study ID Numbers: H9454
First Posted: April 9, 2003    Key Record Dates
Last Update Posted: April 10, 2009
Last Verified: April 2009

Additional relevant MeSH terms:
Virus Diseases
Lymphoproliferative Disorders
Epstein-Barr Virus Infections
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections