Vaccine Therapy in Treating Patients With Stage IV Melanoma

Study Overview
=================
Brief Summary
-----------------
Randomized phase I trial to study the effectiveness of vaccine therapy in treating patients who have stage IV melanoma. Vaccines may make the body build an immune response to kill tumor cells.

Detailed Description
-----------------
OBJECTIVES: I. Determine the dose-limiting toxicities, maximum tolerated dose, recommended phase II dose, and rate of sensitization of T cells at each dose level in patients with melanoma receiving dendritic cell vaccine. II. Determine the overall (complete and partial) response rate, duration of response, and optimal route of administration in this patient population. OUTLINE: This is a dose escalation study. Patients are randomized to one of three treatment arms. All patients undergo leukopheresis to obtain lymphocyte and myeloid origin mononuclear cell fractions for preparation of dendritic cell (DC) vaccine. In each arm, cohorts of up to 5 patients receive escalating doses of vaccine. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 5 patients experience dose-limiting toxicity. Randomization ceases if the MTD has been reached in 2 arms, although accrual may continue. Treatment repeats every 2 weeks for a total of 4 doses. Arm I: Patients receive 3 different doses of peptide pulsed DC vaccine IV, each divided into 3 different peptide pulsed pools administered over 30 minutes. Arm II: Patients receive 3 different doses of peptide pulsed DC vaccine subcutaneously/intradermally to sites with no evidence of disease. At the lowest dose, patients receive 3 different peptide pulsed pools, each administered at a separate site. At the higher doses, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites. Arm III: Patients receive peptide pulsed DC vaccine intranodally in groin or ancillary lymph nodes at the lower 2 doses of the 3 administered to arms I and II. At the lower dose, patients receive 3 different peptide pulsed pools, each administered into a different node. At the higher dose, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites. Patients are followed at 2 weeks and then monthly for 3 months.

Official Title
-----------------
Phase I Trial of a Dendritic Cell Vaccine for Melanoma

Conditions
-----------------
Melanoma (Skin)

Intervention / Treatment
-----------------
* Biological: dendritic cell-MART-1 peptide vaccine
* Biological: gp100 antigen
* Biological: therapeutic tumor infiltrating lymphocytes
* Biological: tyrosinase peptide


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: -Histologically confirmed stage IV melanoma Must be MHC Class I HLA-A2.1 PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-1 Life expectancy: At least 2 months Platelet count at least 100,000/mm3 INR no greater than 1.5 mg/dL No coagulopathies including thrombocytopenia Partial thromboplastin time no greater than 50 seconds No major cardiac illness No major respiratory illness No active systemic infection or other illness No peripheral vascular disease Not pregnant or nursing Effective contraception required of all fertile patients during and for one month after completion of treatment PRIOR CONCURRENT THERAPY: At least 30 days since prior immunotherapy No concurrent immunotherapy At least 30 days since prior chemotherapy No concurrent chemotherapy At least 30 days since prior radiotherapy No concurrent radiotherapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive 3 different doses of peptide pulsed DC vaccine IV, each divided into 3 different peptide pulsed pools administered over 30 minutes. | Biological: dendritic cell-MART-1 peptide vaccine<br> <br> Biological: gp100 antigen<br> <br> Biological: therapeutic tumor infiltrating lymphocytes<br> <br> Biological: tyrosinase peptide<br> <br> |
| Experimental: Arm II<br>Patients receive 3 different doses of peptide pulsed DC vaccine subcutaneously/intradermally to sites with no evidence of disease. At the lowest dose, patients receive 3 different peptide pulsed pools, each administered at a separate site. At the higher doses, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites. | Biological: dendritic cell-MART-1 peptide vaccine<br> <br> Biological: gp100 antigen<br> <br> Biological: therapeutic tumor infiltrating lymphocytes<br> <br> Biological: tyrosinase peptide<br> <br> |
| Experimental: Arm III<br>Patients receive peptide pulsed DC vaccine intranodally in groin or ancillary lymph nodes at the lower 2 doses of the 3 administered to arms I and II. At the lower dose, patients receive 3 different peptide pulsed pools, each administered into a different node. At the higher dose, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites. | Biological: dendritic cell-MART-1 peptide vaccine<br> <br> Biological: gp100 antigen<br> <br> Biological: therapeutic tumor infiltrating lymphocytes<br> <br> Biological: tyrosinase peptide<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV melanoma, recurrent melanoma