Melanoma (Skin)
Conditions
Keywords
stage III melanoma, stage IV melanoma, recurrent melanoma, mucosal melanoma
Brief summary
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic melanoma.
Detailed description
In this phase I study, patients will receive intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC with total volumes for each intradermal injection of no more than 1 ml to be split into four injections of 0.25 ml each in four limbs in node draining areas (proximal arms and thighs), for a total DC dose of 2 X 10\^6, 10\^7 or 2 X 10\^7 cells to be administered intradermally. DC injections in one course of therapy will be given four times at intervals of weekly for two doses (days 1 and 8 +/- 72 hrs.), then every two weeks for two doses (at days 22 +/- 72 hrs. and 36 +/- 72 hours). Cells will be harvested for DC administration and a flow cytometry analysis as well as microbiologic analysis including bacterial/fungal cultures and gram stain will be performed prior to infusion. All injections will be based on number of DC, not number of total cells.
Interventions
Intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC
Sponsors
National Cancer Institute (NCI)
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic melanoma with measurable disease after attempted curative surgical therapy and who have received at least one prior chemotherapy regimen; adjuvant interferon or isolated limb perfusion is allowed. * Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-1 by immunohistochemical staining and will also be stained for HMB-45 by immunohistochemistry, and positivity for at least one will be an entry requirement. * Patients must be HLA-A \*0201 positive, by a DNA SSOP analysis. * Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and ALT/AST of less than 3X institutional upper limit of normal. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Patients must be able to understand and sign an IRB approved informed consent form. * Patients must have white blood count of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more. * Patients with unresectable stages III/IV uveal melanoma and metastatic mucosal melanoma will be eligible for this trial.
Exclusion criteria
* Undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy * Have major systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months * Require steroid therapy * Patients who are pregnant or lactating * Known to be positive for hepatitis BsAg, Hepatitis C or HIV antibody * Have a prior history of uveitis or autoimmune inflammatory eye disease * Have had another malignancy other than cervical carcinoma-in-situ or basal cell /squamous cancer of the skin, unless they have undergone curative therapy more than 3 years ago and are still free of detectable disease, since the effects of peptide-pulsed DC on other active cancers are unknown
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Immune response | 2 years, 5 months | Assessment of immune responses to the cytokine-cocktail-matured class I peptide-pulsed adenoviral CCL-21 transduced DC cell vaccine. Immune reactivity will be monitored for the appearance of lymphoid-like structures at the vaccine site (as a result of CCL-21 production), in the blood for MART-1 /gp100 specific T cell frequency by tetramer based flow cytometry and ELISPOT analysis of fresh cells, and CTL cytolytic reactivity after in vitro sensitization prior to, four weeks after, and 8 weeks after immunization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events | 2 years, 5 months | Toxicity as assessed by NCI CTCAE v3.0 |
Countries
United States
Outcome results
None listed