RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Biological therapies, such as BCG and sargramostim, use different ways to stimulate the immune system and stop tumor cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with BCG and sargramostim in treating patients who have undergone cystectomy for transitional cell cancer of the bladder.

Condition	Treatment or Intervention	Phase
transitional cell carcinoma of the bladder stage I bladder cancer	Drug: BCG  Drug: NY-ESO-1 peptide vaccine  Drug: sargramostim  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the safety and tolerability of NY-ESO-1 peptide vaccine, 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 peptide vaccine mixed with BCG intradermally (ID) once weekly on weeks 1 and 2. Patients then receive NY-ESO-1 peptide 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. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 2 and 6 weeks.

PROJECTED ACCRUAL: A total of 24-28 patients (8 HLA-A2 positive with prior intravesical BCG, 8 HLA-A2 positive without prior intravesical BCG, 4-6 HLA-A2 negative with prior intravesical BCG, and 4-6 HLA-A2 negative without prior intravesical BCG) will be accrued for this study within 15 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the bladder
• Tumor expression of NY-ESO-1 by reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemistry OR LAGE-1 by RT-PCR
• Prior cystectomy within the past 4-16 weeks
• No evidence of disease by radiological imaging within the past month

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Neutrophil count at least 1,500/mm^3
• Lymphocyte count at least 500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL
• No bleeding disorders

Hepatic

• Bilirubin no greater than 2 mg/dL
• AST and ALT less than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.8 mg/dL

Cardiovascular

• No New York Heart Association class III or IV heart disease

Immunologic

• No history of immunodeficiency disease
• No history of autoimmune disease

Other

• HIV negative
• No prior severe reaction to PPD (at least 15 mm induration)
• No other malignancy within the past 5 years that has been treated with extensive chemotherapy/radiotherapy, has the potential for immune dysfunction, or has evidence of metastasis at the time of study entry
• No other serious illness
• No serious infection requiring antibiotics
• No mental disorder that would preclude the ability to give informed consent or comply with study requirements

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior immunotherapy
• No prior bone marrow or peripheral blood stem cell transplantation

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy

Endocrine therapy

• More than 30 days since prior corticosteroids
• No concurrent systemic corticosteroids
• Concurrent topical or inhalational steroids allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 5 days since prior antibiotics
• More than 4 weeks since prior participation in another clinical study
• No concurrent antihistaminic drugs
• No concurrent nonsteroidal anti-inflammatory drugs except low doses for prevention of an acute cardiovascular event or pain control
• No concurrent immunosuppressive agents

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Dean F. Bajorin, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   
Harry W. Herr, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000329920; MSKCC-03047; LUDWIG-LUD2002-004; NCT00070070
Record last reviewed:  September 2003
Last Updated:  December 6, 2004
Record first received:  October 3, 2003
ClinicalTrials.gov Identifier:  NCT00070070
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08