RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may kill more tumor cells.

PURPOSE: Randomizedphase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have metastaticmelanoma.

Condition	Treatment or Intervention	Phase
stage III melanoma Stage IV Melanoma Recurrent Melanoma	Drug: MAGE-10.A2  Drug: Melan-A  Drug: NY-ESO-1 peptide vaccine  Drug: sargramostim  Drug: tyrosinase peptide  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Compare the safety of melanoma peptide vaccine with or without sargramostim (GM-CSF) in patients with high-risk or metastatic melanoma.
• Compare changes in peptide-specific cellular and humoral immunologic profiles in patients treated with these regimens.
• Compare tumor response in patients treated with these regimens.

OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive melanoma peptide vaccine comprising tyrosinase leader injected at 2 separate sites, Melan-A ELA injected at another site, NY-ESO-1a and NY-ESO-1b combined and injected at one site, and MAGE-10.A2 injected at another site, intradermally once weekly on weeks 1-6.
• Arm II: Patients receive vaccine as in arm I. Patients also receive sargramostim (GM-CSF) subcutaneously daily beginning 2 days before each vaccination and continuing for 5 days. Treatment in both arms continues through week 6 in the absence of disease progression or unacceptable toxicity.

Patients are followed at 2 weeks.

PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study within 18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed high-risk stage III or IV melanoma
• Stage III disease less than 6 months after surgical resection
• Completed prior interferon alfa therapy OR
• Progressive disease or major adverse events during prior interferon alfa therapy
• Stage III disease at least 6 months after surgical resection
• Declined, failed, or completed prior standard therapy
• Stage IV disease
• Declined, failed, or completed prior standard therapy
• HLA-A2 positive
• No CNS metastases unless treated and stable

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 80-100%

Life expectancy:

• At least 4 months

Hematopoietic:

• Neutrophil count at least 1,500/mm3
• Lymphocyte count at least 500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 9.0 g/dL (10.0 g/dL if less than 50 kg)
• No bleeding disorder

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• No hepatitis B or C positivity

Renal:

• Creatinine no greater than 1.8 mg/dL

Cardiovascular:

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

Other:

• HIV negative
• No other serious illness
• No serious infection requiring antibiotics
• No history of immunodeficiency disease or autoimmune disease
• No psychiatric or addictive disorder that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• No prior bone marrow or stem cell transplantation
• At least 4 weeks since prior immunotherapy or biologic therapy
• No other concurrent immunotherapy or biologic therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent systemic corticosteroids
• No concurrent steroids except topical or inhalational steroids
• Concurrent hormonal therapy allowed

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior surgery

Other:

• At least 4 weeks since prior investigational agents
• Concurrent noncytotoxic anticancer therapy allowed
• No concurrent immunosuppressive therapy
• No concurrent antihistamines
• No concurrent non-steroidal anti-inflammatory drugs except in low doses for prevention of an acute cardiovascular event or pain control

New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States

Study chairs or principal investigators

Kyriakos P. Papadopoulos, MD,  Study Chair,  Columbia University   

Study ID Numbers:  CDR0000069357; CPMC-IRB-13824; LUDWIG-LUD00-025; NCI-G02-2068
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  May 13, 2002
ClinicalTrials.gov Identifier:  NCT00037037
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08