Comparison Study of Dendritic Cell Vaccine With and Without Cyclophosphamide to Treat Stage IV Melanoma Patients

Inclusion Criteria:

Biopsy-proven metastatic melanoma, Stages M1a, M1b, M1c
HLA-A*0201 phenotype
Age: 21-75 years
ECOG performance status 0-1
Measurable metastatic melanoma lesions by physical examination or radiographs or scans.

Adequate marrow function:

White count ≥ 4,000/microliter: Subjects who have recently completed chemotherapy will be allowed study entry with White count ≥ 3,500/microliter
Hemoglobin ≥ 10.0 gm: Subjects who have recently completed chemotherapy will be allowed study entry with Hemoglobin ≥ 9.0 gm.
Platelets ≥ 100,000/microliter

Adequate hepatic function:

Bilirubin ≤ 1.5/mg/dL
Alkaline phosphatase ≤ 5 times the upper limit of normal
SGOT ≤ 5 times the upper limit of normal
SGPT ≤ 5 times the upper limit of normal

Adequate renal function:

Serum creatinine ≤ 1.5/mg/dL

No active CNS metastatic disease at screening.

Patients with a history of CNS melanoma lesions must have had lesions resected by surgery and/or gamma knife irradiation at least 3 months prior to study entry.
The total number of CNS lesions at diagnosis should not have exceeded 3.
Written informed consent

Exclusion Criteria:

Patients who have received > 8 cycles of cytotoxic chemotherapy or metastatic melanoma
Patients who have received any chemotherapy < 4 weeks before the beginning of the trial
Patients who have received interferon alpha (IFNα-2b) or sargramostim (GM-CSF) < 4 weeks before the beginning of the trial
Patients who have received high-dose interleukin-2 (IL-2) < 4 weeks before the beginning of the trial
Patients that have been diagnosed with more than 3 CNS melanoma lesions.
Patients that have been diagnosed with more than 5 hepatic metastases or any hepatic metastasis > 5 cm.
Baseline serum LDH > 1.1 times the upper limit of normal
Patients who are HIV+ (HIV patients are often profoundly immunodeficient because of the viral infection and this additional parameter will interfere with the evaluation of DC induced immune responses in melanoma patients. Furthermore, the safety of collecting DCs, loading them with antigen and re-infusing these cells to HIV+ patients has not yet been determined.)
Pregnancy (Pregnancy is associated with considerable immunosuppression 70 and this additional parameter will interfere with the evaluation of DC induced immune responses in melanoma patients. In addition, the safety and tolerability of cell body-loaded DC given subcutaneously is entirely unknown.)
Patients who have received corticosteroids or other immunosuppressive agents < 4 weeks before beginning the trial
Patients with active asthma and/or on treatment for asthma
Patients with angina pectoris
Patients with congestive heart failure
Patients with a history of autoimmune disease including lupus erythematosus, rheumatoid arthritis or thyroiditis
Patients with active infections including viral hepatitis
Patients with a history of neoplastic disease other than melanoma < 5 years prior to entry on the trial except for patients with carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin. Patients who have any of these two types of cancer and melanoma can be included.