Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00058604
First received: April 8, 2003
Last updated: April 9, 2009
Last verified: April 2009

April 8, 2003
April 9, 2009
January 2001
December 2008   (final data collection date for primary outcome measure)
  • Generate autologous, EBV-specific, cytotoxic T cell lines (CTLs) from individuals receiving or having received a solid organ transplant (SOT). [ Time Frame: pre-treatment ] [ Designated as safety issue: No ]
  • Administer autologous, EBV-specific CTLs to patients, to determine the safety of intravenous injections in these individuals [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Evaluate the antiviral and immunological efficacy of the infused CTLs [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00058604 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Prevention and Treatment of Epstein-Barr Virus (EBV) Lymphoma Following a Solid Organ Transplant Using EBV Specific Cytotoxic T Lymphocytes (CTLs).
Autologous EBV Specific CTLs for Prophylaxis and Therapy of EBV Lymphoma Post Solid Organ Transplant

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

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Epstein-Barr Virus Infections
  • Lymphoproliferative Disorders
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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
December 2008
December 2008   (final data collection date for primary outcome measure)

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.
Both
up to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00058604
H9454, Euclid
Yes
Helen Heslop, Baylor College of Medicine
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
Baylor College of Medicine
April 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP