Reduced Immunosuppressive Therapy With or Without Donor White Blood Cells in Treating Patients With Lymphoproliferative Disease After Organ Transplantation

University of Edinburgh

Status and phase: Completed; Phase 3

Conditions: Lymphoproliferative Disorder

Treatments: Biological: therapeutic allogeneic lymphocytes

Study type: Interventional

Funder types: Other

Identifiers

NCT00033475

LCMV-CTL

CRUK-EBV-CTL

EU-20057

CDR0000069288

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 50 estimated patients

Sex: All

Ages: Under 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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