RATIONALE: Some types of lymphoproliferative disease are associated with Epstein-Barr virus. Combining reduced immunosuppressive therapy with donor white blood cells that have been treated in the laboratory to kill cells infected with Epstein-Barr virus may be an effective treatment for lymphoproliferative disease.

PURPOSE: Randomized phase III trial to compare the effectiveness of reducing immunosuppressive therapy with or without donor white blood cells in treating patients who have Epstein-Barr virus-associated lymphoproliferative disease after organ transplantation.

Condition	Treatment or Intervention	Phase
post-transplant lymphoproliferative disorder	Drug: EBV-specific cytotoxic T-lymphocytes  Procedure: biological response modifier therapy  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of treatment with partially HLA-matched allogeneic cytotoxic T cells and reduction of immunosuppression, in terms of survival rate and time to remission in patients with Epstein-Barr virus-associated B-cell lymphoproliferative disease after solid organ transplantation.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to transplanted organ type and transplant center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo sliding-scale reduction of immunosuppressive drugs from 1 of 5 regimens at physician's discretion. Patients then receive partially HLA-matched allogeneic cytotoxic T cells IV over 5 minutes once weekly for a total of 4 weeks.
• Arm II: Patients undergo reduction of immunosuppression as in arm I alone. Patients are followed monthly for 6 months and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of post-transplant lymphoproliferative disease (PTLD) after solid organ (heart, heart/lung, liver, liver/gut, pancreas, or kidney) transplantation
• Epstein-Barr virus-positive tumor
• Newly diagnosed disease
• Measurable disease by clinical methods or radiography
• Must have partially matched donor cytotoxic T cells (CTL) available
• No known panel reactivity to any of the HLA types of CTL available for therapy

PATIENT CHARACTERISTICS: Age:

• Any age

Performance status:

• Karnofsky 20-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No prior therapy for PTLD
• No concurrent antiviral drugs (e.g., acyclovir or ganciclovir) for PTLD

United Kingdom, England
      Birmingham Children's Hospital, Birmingham,  England,  B4 6NH,  United Kingdom; Recruiting
      Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester,  England,  M27 4HA,  United Kingdom; Recruiting
      Institute of Cancer Research - UK, Sutton,  England,  SM2 5NG,  United Kingdom; Recruiting
      King's College Hospital, London,  England,  SE5 8RX,  United Kingdom; Recruiting
      Northern General Hospital, Sheffield,  England,  S5 7AU,  United Kingdom; Recruiting
      Papworth Hospital, Cambridge,  England,  CB3 8RE,  United Kingdom; Recruiting
      Royal Free and University College Medical School, London,  England,  NW3 2PF,  United Kingdom; Recruiting
      Wythenshawe Hospital, Manchester,  England,  M23 9LJ,  United Kingdom; Recruiting
United Kingdom, Scotland
      Royal Infirmary - Castle, Glasgow,  Scotland,  G4 0SF,  United Kingdom; Recruiting
      Royal Infirmary of Edinburgh at Little France, Edinburgh,  Scotland,  EH16 4SA,  United Kingdom; Recruiting
      University of Edinburgh Laboratory for Clinical and Molecular Virology, Edinburgh,  Scotland,  EH9 1QH,  United Kingdom; Recruiting
      University of Edinburgh Medical School, Edinburgh,  Scotland,  EH8 9XD,  United Kingdom; Recruiting

Study chairs or principal investigators

Dorothy H. Crawford, MD,  Study Chair,  University of Edinburgh Medical School   

Study ID Numbers:  CDR0000069288; CRUK-EBV-CTL; LCMV-CTL; EU-20057; NCT00033475
Record last reviewed:  May 2003
Last Updated:  April 4, 2005
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033475
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08