Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas

OBJECTIVES:

• Determine the safety and tolerability of NY-ESO-1 peptide vaccine, Bacille Calmette Guerin (BCG), and sargramostim (GM-CSF) in post-cystectomy patients with transitional cell carcinoma of the bladder expressing NY-ESO-1 or LAGE-1 antigen.
• Determine the immunological profile (NY-ESO-1 antibody, CD8+ cells, and delayed-type hypersensitivity) induced by this regimen in these patients.

OUTLINE: This is an open-label, pilot study.

Patients receive NY-ESO-1 protein vaccine mixed with BCG intradermally (ID) once weekly on weeks 1 and 2. Patients then receive NY-ESO-1 protein mixed with sargramostim (GM-CSF) ID once weekly on day 2 of weeks 3-6. Patients also receive GM-CSF subcutaneously alone on days 1, 3, 4, and 5 of weeks 3-6.

Inclusion criteria

• Post-cystectomy or post-nephroureterectomy patients with histological confirmation of transitional cell carcinoma.
• Patients must have had a cystectomy or nephroureterectomy within 16 weeks of first vaccination.
• At least 4 weeks since surgery prior to receiving the first vaccination.
• Radiological imaging to document no evidence of disease within one month prior to receiving the first vaccination.
• Laboratory values within the following limits:

Hemoglobin ≥ 10.0 g/dL Neutrophil count ≥ 1.5 x 10E9/L Lymphocyte count ≥ 0.5 x 10E9/L Platelet count ≥ 100 x 10E9/L Serum creatinine ≤ 1.8 mg/dL Serum bilirubin ≤ 2mg/dL Serum aspartate aminotransferase (AST) (SGOT) <2.5 X ULN Serum alanine aminotransaminase (ALT) (SGPT) <2.5 X ULN 6. Performance status ≤ 2 (ECOG Scale) and life expectancy ≥ 3 months. 7. Age ≥ 18 years. 8. Fertile patients must have a negative urine or serum pregnancy test and use barrier method contraception before, during and for 6 months after protocol therapy. Patients are encouraged to continue barrier method contraception for two years or longer after treatment.

• Able and willing to give valid written informed consent. Exclusion Criteria

• Clinically significant heart disease (NYHA Class III or IV).
• Presence of severe reaction to PPD (purified protein derivative) (>40 mm induration).
• Prior malignancy within 5 years that has been treated with extensive chemotherapy / radiation therapy and have the potential for immune dysfunction or who have evidence of metastasis at the time of registration.
• Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, antibiotic use within 5 days of treatment.
• Previous bone marrow or stem cell transplant.
• History of immunodeficiency disease or autoimmune disease.
• Known positive HIV test.
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
• Concomitant treatment with corticosteroids (within 30 days of enrollment and during treatment), antihistaminic drugs, or nonsteroidal anti-inflammatory drugs (unless chronically used in low doses for prevention of an acute cardiovascular event or pain control). Topical or inhalational steroids are permitted.
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
• Mental disorders that may compromise the ability to give informed consent and comply with the requirements of the study.
• Lack of availability of the patient for immunological and clinical follow-up assessment.
• Positive urine or serum pregnancy test.