Allogeneic Epstein Barr Virus-Specific Cytotoxic T-Lymphocytes in Treating Patients With Progressive, Relapsed, or Refractory Hodgkin's Lymphoma

A Phase I Pilot Trial to Evaluate the Toxicity of Epstein-Barr Virus Specific T-Lymphocytes or Peripheral Blood Mononuclear Cells for the Treatment of Relapsed/Refractory Hodgkin's Disease

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Donor white blood cells that are treated in the laboratory with Epstein-Barr virus may be effective treatment for Hodgkin's lymphoma.

PURPOSE: Phase I trial to study the effectiveness of allogeneic Epstein-Barr virus-specific cytotoxic T cells in treating patients who have progressive, relapsed, or refractory Hodgkin's lymphoma.

OBJECTIVES:

• Determine the toxicity of allogeneic Epstein Barr virus (EBV)-specific cytotoxic T-lymphocytes (EBV CTL) in patients with progressive, relapsed, or refractory EBV-positive Hodgkin's lymphoma.
• Detect alterations in the anti-EBV cellular immunity of patients treated with EBV CTL.

OUTLINE: Donors undergo leukapheresis. Epstein Barr virus-specific cytotoxic T lymphocytes (EBV CTL) are cultured in vitro.

Patients receive an infusion of EBV CTL over 10 minutes on day 0. The EBV CTL infusion is preceded by 3 doses of fludarabine. Patients then receive interleukin-2 injections for 12 days after the EBV CTL infusion.

Patients are followed weekly for 1.5 months, twice a month for 1.5 months, and then monthly for 3 months.

PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven Hodgkin's lymphoma

  • Progressive, relapsed, or refractory disease after prior chemotherapy, radiotherapy, and/or stem cell transplantation
  • Epstein Barr virus (EBV) positive by immunohistochemical staining for LMP-1 or 2 OR the presence of EBV RNA (EBER)

• Availability of an HLA identical or haploidentical donor for cytotoxic T-lymphocytes, meeting the following criteria:

  • EBV seropositive
  • HIV negative
  • HTLV-1 negative
  • Hepatitis B surface antigen and hepatitis B core antibody IgM negative
  • Hepatitis C antibody negative
  • Must share at least 1 HLA haplotype with donor

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• Not specified

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2.0 mg/dL

• SGOT/SGPT less than 2.5 times normal (unless liver metastases are present)

  • If there is liver involvement by disease, an obvious relationship between SGOT/SGPT and disease activity is required

• No hepatic dysfunction causing moribundity

Renal:

• Creatinine clearance greater than 50 mL/min
• No renal dysfunction causing moribundity

Cardiovascular:

• No cardiac dysfunction causing moribundity

Pulmonary:

• No pulmonary dysfunction causing moribundity

Other:

• No neurologic dysfunction causing moribundity
• No history of severe transfusion reactions with blood products (including fetal calf serum)
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• No concurrent antimetabolites

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified