Melanoma Peptide-Loaded Dendritic Cell Vaccine in HLA-A*0201 Patients With Stage IV Melanoma: A Phase II Randomized Trial to Compare Vaccination With and Without Cyclophosphamide Treatment.
1. Biopsy-proven metastatic melanoma, Stages M1a, M1b, M1c
2. HLA-A*0201 phenotype
3. Age: 21-75 years
4. ECOG performance status 0-1
5. Measurable metastatic melanoma lesions by physical examination or radiographs or
6. 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
7. 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
8. Adequate renal function:
- Serum creatinine ≤ 1.5/mg/dL
9. 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
- The total number of CNS lesions at diagnosis should not have exceeded 3.
10. Written informed consent
1. Patients who have received > 8 cycles of cytotoxic chemotherapy or metastatic
2. Patients who have received any chemotherapy < 4 weeks before the beginning of the
3. Patients who have received interferon alpha (IFNα-2b) or sargramostim (GM-CSF) < 4
weeks before the beginning of the trial
4. Patients who have received high-dose interleukin-2 (IL-2) < 4 weeks before the
beginning of the trial
5. Patients that have been diagnosed with more than 3 CNS melanoma lesions.
6. Patients that have been diagnosed with more than 5 hepatic metastases or any hepatic
metastasis > 5 cm.
7. Baseline serum LDH > 1.1 times the upper limit of normal
8. 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.)
9. 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.)
10. Patients who have received corticosteroids or other immunosuppressive agents < 4
weeks before beginning the trial
11. Patients with active asthma and/or on treatment for asthma
12. Patients with angina pectoris
13. Patients with congestive heart failure
14. Patients with a history of autoimmune disease including lupus erythematosus,
rheumatoid arthritis or thyroiditis
15. Patients with active infections including viral hepatitis
16. 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.