Vaccine Therapy in Treating Patients With Stage IV or Relapsed Malignant Melanoma

OBJECTIVES:

- Determine the safety of administering MART-1 peptide-pulsed dendritic cells to patients
with stage IV or relapsed malignant melanoma.

- Determine the immunological and clinical responses in this patient population after
this therapy.

OUTLINE: This is a dose-escalation study.

Patients undergo leukapheresis between days -14 to -8. Mononuclear cells are isolated, used
to generate dendritic cells (DC), and then pulsed with MART-1 peptide. Patients are
vaccinated with MART-1 peptide-pulsed DC either IV or intradermally on days 0, 14, and 28.

Cohorts of 3-6 patients receive escalating doses of MART-1 peptide-pulsed DC until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed until death.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study.

Inclusion Criteria:

- Adults over the age of 18 with malignant melanoma.

- HLA-A2.1 positive and express MART-1, as assessed by either RT-PCR or by
immunohistochemistry

- Tumor stages T3N0M0 or greater are eligible for this trial according to the
following:

1. I (<.75 to 1.5 mm or Clark level III-T1-2N0M0-)—not eligible

2. II (1.5 to 4 mm or level IV-T3N0M0-)—eligible

3. III (limited nodal metastasis involving one regional lymph node basin, or fewer
than 5 in-transit metastasis -TxN1M0-)—eligible

4. IV (advanced regional metastasis -TxN2M0- or any distant metastasis
-TxNxM1-)—eligible

5. Relapsed melanoma—eligible

- Patients previously treated with any form of therapy for either metastatic, relapsed
or primary melanoma are eligible for this trial, provided that previous treatment was
completed >30 days prior to enrollment

- Both male and females may be enrolled. Premenopausal females must have a negative
pregnancy test prior to treatment

- Karnofsky Performance Status greater than or equal to 70 percent

- No previous evidence of class 3 or greater New York Heart Association cardiac
insufficiency or coronary artery disease

- No previous evidence of opportunistic infection

- A minimum of 30 days must have elapsed since the completion of prior chemotherapy,
immunotherapy or radiation therapy

- Adequate baseline hematological function as assessed by the following laboratory
values within 30 days prior to study entry (day -30 to 0):

1. Hemoglobin >9.0 g/dl

2. Platelets > 100000/mm3

3. WBC > 3000/mm3

4. Absolute Neutrophil Count > 1000/mm3

- Positive skin test to common antigens (tetanus and candida)

- Ability to give informed consent

Exclusion Criteria:

- Lactating females and females of child-bearing potential must have negative serum
beta-HCG pregnancy test

- Acute infection: any acute viral, bacterial, or fungal infection which requires
specific therapy. Acute therapy must have been completed within 14 days of prior to
study treatment

- HIV-infected patients

- Acute medical problems such as ischemic heart or lung disease that may be considered
an unacceptable anesthetic or operative risk

- Patients with any underlying conditions which would contraindicate therapy with study
treatment (or allergies to reagents used in this study)

- Patients with organ allografts

- Uncontrolled CNS metastasis. Patients with CNS metastasis will be eligible if they
have received CNS irradiation to control local tumor growth