Randomized Phase II Evaluation of Immunization Against Tumor Cells in Subjects With Metastatic Melanoma Using Autologous Mature Dendritic Cells

Inclusion Criteria:

- Subjects must have Stage III-IV melanoma (any tumor thickness and any number of lymph
node involvement, and in-transit metastases, or distant metastases) (AJCC). Each
diagnosis will be confirmed by pathology review at the Melanoma Center of the
University of Pittsburgh Cancer Institute.

- All subjects have to be HLA-A2 positive (required for immunologic testing).

- Subjects must have recovered fully from surgery.

- Availability of resectable or tissue banked tumor cells for autologous tumor
dendritic cell vaccine preparation.

- Sufficient number of tumor cells available for autologous tumor dendritic cell
vaccine preparation (min 2.6 x 10 7).

- Sufficient number of DCs of at least 12 X 10 6 for preparation of the autologous
tumor dendritic cell vaccine preparation (if less than needed number of cells will be
obtained by one course of leukopheresis, the second leukopheresis will be repeated 2
weeks apart).

- Subjects must not have received any chemotherapy or immunotherapy within the four
weeks preceding vaccination (six weeks for nitrosourea, mitomycin).

- Subjects must have an expected survival of greater than or equal to 12 months.

- Subjects must have an ECOG performance status 0 or 1.

- Subjects must have the following initial and subsequent pretreatment

- laboratory parameters: Granulocytes >=2,500/mm3 Lymphocytes >=1000/mm3 Platelets
>100,000/mm3 Serum Creatinine <=1.5 X the ULN AST, ALT, GGT, LDH, Alk phos <= 2.5 X
the ULN Serum Bilirubin <=1.5 X ULN

- Subjects must be >= 18 years of age and must be able to understand the written
informed consent.

- No evidence of active infection, regardless of the degree of severity or
localization. Subjects with active infections (whether or not they require
antibiotic therapy) may be eligible after complete resolution of the infection.
Subjects on antibiotic therapy must be off antibiotics for at least 7 days before
beginning treatment.

- Subjects with measurable disease must have an evaluation for extent of disease (tumor
staging) performed within 30 days of start of treatment.

- Pretreatment baseline evaluations for laboratory parameters must be obtained within
10 to18 days of subject registration

Exclusion Criteria:

- Subjects currently treated with anti inflammatory agents including glucocorticoid
therapy are ineligible.

- Subjects currently on treatment with steroids are ineligible, but may receive the DC
autologous tumor dendritic cell vaccine 4 weeks after steroid cessation. Subjects on
maintenance steroids because of adrenal insufficiency are eligible.

- Subjects with severely abnormal liver function tests [AST (SGOT), ALT (SGPT), GGT,
Alk.Phos, LDH, and total bilirubin greater than 2 X ULN].

- Subjects with uncontrolled pain.

- Subjects with autoimmune disease, HIV, and hepatitis

- Subjects with symptomatic brain metastasis.

- Subjects with active prior malignancy (with exception of non-melanoma skin cancers
and carcinoma in situ of the cervix).

- Subjects who have been previously immunized with melanoma vaccine until 10 subjects
have been registered in each treatment arm.

- Subjects who are pregnant.

- Subjects who have sensitivity to drugs to provide local anesthesia.