• Maximum tolerated dose of autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in combination with anti-CD45 monoclonal antibody [ Designated as safety issue: Yes ]
• Safety [ Designated as safety issue: Yes ]
• Changes in laboratory data at baseline, 2, 4, 6, and 8 weeks and at 3 months [ Designated as safety issue: No ]
• Extent and duration of immune depletion at pre-antibody infusion, pre-CTL infusion, 4 hours after infusion on days 3 and 4, and at 1, 2, 4, 6, and 8 weeks post-CTL infusion [ Designated as safety issue: No ]

• Maximum tolerated dose of autologous Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) in combination with anti-CD45 monoclonal antibody [ Designated as safety issue: Yes ]
• Safety [ Designated as safety issue: Yes ]
• Changes in laboratory data at baseline, 2, 4, 6, and 8 weeks and at 3 months [ Designated as safety issue: No ]
• Extent and duration of immune depletion at pre-antibody infusion, pre-CTL infusion, 4 hours after infusion on days 3 and 4, and at 1, 2, 4, 6, and 8 weeks post-CTL infusion [ Designated as safety issue: No ]

• Immunologic function as measured by interferon-gamma, percentage of tetramer-positive cells in peripheral blood, and EBV-DNA in plasma [ Designated as safety issue: No ]
• Frequency of T-cells specific for CMV antigens (or for adenovirus in CMV-seronegative individuals) and EBV antigens at each time point of follow-up [ Designated as safety issue: No ]
• Correlation between endogenously reconstituted versus adoptively transferred T-cells [ Designated as safety issue: No ]
• Overall response rate [ Designated as safety issue: No ]

• Immunologic function as measured by interferon-gamma, percentage of tetramer-positive cells in peripheral blood, and EBV-DNA in plasma [ Designated as safety issue: No ]
• Frequency of T-cells specific for CMV antigens (or for adenovirus in CMV-seronegative individuals) and EBV antigens at each time point of follow-up [ Designated as safety issue: No ]
• Correlation between endogenously reconstituted versus adoptively transferred T cells [ Designated as safety issue: No ]
• Overall response rate [ Designated as safety issue: No ]

RATIONALE: White blood cells that are treated in the laboratory with Epstein-Barr virus may help the body build an effective immune response to kill tumor cells. Biological therapies, such as anti-CD45 monoclonal antibody, may stimulate the immune system in different ways and help to stop tumor cells from growing. Giving T lymphocytes treated in the laboratory together with anti-CD45 monoclonal antibody may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of T lymphocytes given after anti-CD45 monoclonal antibody in treating patients with Epstein-Barr virus-positive nasopharyngeal cancer.

OBJECTIVES:

Primary

• To determine the safety of autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in combination with anti-CD45 monoclonal antibody (Mab) in patients with nasopharyngeal cancer.
• To obtain information on the expression, persistence, and anti-tumor effects of EBV-specific CTL lines given after lymphodepletion with anti-CD45 Mab in these patients.
• To obtain preliminary information on the safety and response to an extended dosage regimen of EBV-specific CTL in patients who have stable disease or a partial response after the initial dose of EBV-specific CTL.

OUTLINE: This is a dose-escalation study of autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTL).

Patients undergo peripheral blood collection for the generation of EBV-specific CTL. Patients receive anti-CD45 monoclonal antibody (Mab) IV over 6-8 hours on days 1-4. Approximately 2-4 days later (when the anti-CD45 Mab level is < 100 μg/mL), patients receive 1 dose (dose is escalated in different patient cohorts) of EBV-specific CTL IV over 1-10 minutes. Patients achieving stable disease or partial response at 8-weeks or subsequent evaluations are eligible to receive up to 6 additional doses of EBV-specific CTL at 6-12 week interval.

Patients undergo blood sample collection periodically for immune function studies and plasma free CD45 antibody levels.

After completion of study treatment, patients are followed every 2 weeks for 8 weeks and then at 3, 6, 9, and 12 months.

• Biological: anti-CD45 monoclonal antibody
• Biological: autologous Epstein-Barr virus-specific cytotoxic T lymphocytes

DISEASE CHARACTERISTICS:

• Diagnosis of nasopharyngeal carcinoma meeting any 1 of the following criteria:

  • First or subsequent relapse disease
  • Primary refractory disease
  • High-risk disease (T3 or T4, or node-positive disease)
• EBV genome or antigens demonstrated in tissue biopsies (EBV-positive)

PATIENT CHARACTERISTICS:

• Karnofsky performance status ≥ 50%
• Life expectancy > 6 weeks
• Hemoglobin > 8.0 g/dL
• Bilirubin < 2 times normal
• SGOT < 3 times normal
• Creatinine < 2 times normal for age
• Not pregnant
• Fertile patients must use effective contraception (male partner should use a condom)
• No severe intercurrent infection

PRIOR CONCURRENT THERAPY:

• At least 1 month since prior investigational therapy

• No other anti-neoplastic agents for ≥ 1 month post-CTL infusion

  • Patients may receive other therapy if needed at the discretion of the attending physician