Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies

• Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  
• Potential of adoptive immunotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  
• In vivo biodistribution, expansion, and duration of engraftment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  
• Incidence, kinetics, and durability of pathological and/or clinical responses [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the toxicity and therapeutic potential of adoptive immunotherapy with Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes derived from HLA-histocompatible related donors or haplotype-matched donor in the treatment of patients at high-risk or with EBV-induced lymphomas and other lymphoproliferative diseases or malignancies in immunocompromised hosts.
• Complete a single selected dose level phase II extension of this study to identify the probability of achieving a CR of EBV lymphoma with EBV-specific T-cell therapy in allogeneic HSCT recipients and immunodeficient patients.
• Evaluate in vivo biodistribution, expansion, and duration of engraftment of successive doses of EBV-reactive lymphocytes within immunocompromised histocompatible hosts with EBV-associated lymphoproliferative diseases, and correlate these findings with the patients' T-cell populations, general immune status, and capacity to generate allospecific antidonor response.
• Determine incidence, kinetics, and durability of pathologic and/or clinical responses in this patient population treatment with infusions of these EBV-specific T cells.

OUTLINE: This is a dose-escalation study. Patients are stratified according to graft vs host disease risk (high vs low).

Patients receive adoptive immunotherapy with allogeneic Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes IV on days 1, 8, and 15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

The dose of allogeneic EBV-specific cytotoxic T lymphocytes is escalated in cohorts of 3-6 patients until the maximum-tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically for 1 year.