RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have stage III or stage IV melanoma at high risk for recurrence following surgery to remove the tumor.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma stage III melanoma Recurrent Melanoma	Drug: alum adjuvant  Drug: monoclonal antibody 4B5 anti-idiotype vaccine  Drug: sargramostim	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the toxicity of the human anti-idiotypic monoclonal antibody vaccine (4B5) plus adjuvant sargramostim (GM-CSF) or alum in patients with stage III or IV melanoma at high risk for recurrence following surgical resection.

II. Determine whether 4B5 is associated with the development of humoral and/or cellular anti-anti-idiotypic immune response in these patients.

III. Determine whether the immune response generated against 4B5 is also directed against the melanoma-associated GD2 antigen in these patients.

IV. Determine whether the 4B5 plus adjuvant GM-CSF or alum can elicit an immune response to GD2 in these patients.

PROTOCOL OUTLINE: Patients are assigned sequentially to one of two treatment arms.

Arm I: Patients receive human anti-idiotypic monoclonal antibody vaccine (4B5) in sargramostim (GM-CSF) subcutaneously (SQ) on days 0, 14, 28, and 42. Patients receive GM-CSF alone SQ at vaccination site on days 2, 3, and 4 following immunization.

Arm II: Patients receive 4B5 plus alum SQ on days 0, 14, 28, and 42.

Cohorts of 5 patients receive treatment every 2 weeks for up to 4 courses in the absence of unacceptable toxicity.

PROJECTED ACCRUAL: A maximum of 50 patients (25 per arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Pathologically proven stage III or IV melanoma at high risk for recurrence following surgical resection
• The following patients are eligible: Resected satellite or intransit metastasis with no evidence of residual disease OR Resected solitary metastatic lesion(s) with no residual disease OR Metastatic melanoma with measurable disease without noncutaneous lesion(s) greater than 5 cm in diameter OR Stage III disease not eligible for interferon alfa therapy
• No active CNS disease

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; No concurrent immunotherapy
• Chemotherapy: At least 6 weeks since prior chemotherapy and recovered; No more than 1 prior chemotherapy regimen as adjuvant or for metastatic disease; No concurrent chemotherapy
• Endocrine therapy: At least 2 weeks since prior glucocorticoids; No concurrent systemic corticosteroids
• Radiotherapy: At least 4 weeks since prior radiotherapy and recovered; No concurrent radiotherapy
• Surgery: See Disease Characteristics
• Other: At least 30 days since other prior investigational drugs; No concurrent immunosuppressive therapy (e.g., cimetidine); No concurrent chronic antihistamine therapy

--Patient Characteristics--

• Age: Over 18
• Performance status: Karnofsky 70-100%
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin less than 1.5 mg/dL
• Renal: BUN less than 30 mg/dL; Creatinine less than 2 mg/dL
• Other: Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception; HIV negative; No prior or concurrent active peripheral neuropathy; No immunodeficiency disorder or immunodeficiency state; No other prior or concurrent malignancy, except: Curatively treated basal or squamous cell skin cancer; Carcinoma in situ of the cervix; No hypersensitivity to GM-CSF, yeast derived products, or any study component

Study chairs or principal investigators

Donald Max Miller,  Study Chair,  UAB Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067424; UAB-9746; NCI-G99-1644; UAB-F980729009
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  January 21, 2000
ClinicalTrials.gov Identifier:  NCT00004184
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08