A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens
A Phase I, Dose Escalation Trial of Recombinant Modified Vaccinia Ankara (MVA)-Based Vaccine Encoding Epstein-Barr Virus Target Antigens
RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with Epstein-Barr virus and cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive EBNA1 C-terminal/LMP2 chimeric protein-expressing recombinant modified vaccinia Ankara vaccine intradermally on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for immune function, biomarker, and pharmacological studies.
After completion of study treatment, patients are followed up at weeks 11 and 14, and at 6 months and 1 year.
DISEASE CHARACTERISTICS:
Histologically confirmed malignancy of a type typically associated with Epstein-Barr virus (EBV) latent infection meeting the following criteria:
Patients in remission from disease or with disease for which no standard treatment is appropriate, as defined by 1 of the following groups:
Completed standard therapy for malignancy ≥ 12 weeks before trial entry
No ongoing toxic manifestations of prior treatment, except alopecia or certain grade 1 toxicities at the discretion of the investigator and Cancer Research UK
No patients with active EBV+ cancer for whom evidence-based active treatment is available and likely to be offered to prolong life or relieve symptoms within 14 weeks of the first vaccination
PATIENT CHARACTERISTICS:
WHO performance status 0 or 1
Life expectancy ≥ 4 months
Lymphocyte count must satisfy 1 of the following criteria:
Hemoglobin > 10.0 g/dL
Absolute neutrophil count ≥ 1.5 x 10^9/L
Platelet count ≥ 100 x 10^9/L
Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
Serum alkaline phosphatase < 1.5 times ULN
ALT and/or AST < 1.5 times ULN
Calculated creatinine clearance > 50 mL/min (uncorrected value) OR isotope clearance measurement > 50 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during study and for 6 months after completion of study treatment
No known chronic active infection with hepatitis B, hepatitis C, or HIV
No history of anaphylaxis or severe allergy to vaccinations
No allergy to eggs or egg products
No ongoing active infection
No known splenic dysfunction
No concurrent active autoimmune disease
No prior NYHA class III or IV cardiac disease or concurrent congestive heart failure
No concurrent active skin diseases requiring therapy (i.e., psoriasis, eczema)
No other condition that, in the Investigator's opinion, would make the patient not a good candidate for this clinical trial
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior myeloablative therapy followed by an autologous or allogeneic hematopoietic stem cell transplant
More than 12 weeks since prior and no concurrent chemotherapy or radiotherapy
No splenectomy or splenic irradiation
No concurrent immunosuppressive medication, including corticosteroids
No major thoracic and/or abdominal surgery within the past 4 weeks from which the patient has not yet recovered
No other concurrent anticancer or investigational drugs