Vaccine Therapy in Treating Patients With Stage IV Cutaneous Melanoma
RATIONALE: Vaccines made from a person's dendritic cells and antigens may make the body build an immune response to kill tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy using autologous dendritic cells with antigens in treating patients who have stage IV cutaneous melanoma.
Biological: MART-1 antigen
Biological: keyhole limpet hemocyanin
Biological: recombinant MAGE-3.1 antigen
Biological: survivin antigen
Biological: therapeutic autologous dendritic cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Vaccination of Stage IV Cutaneous Melanoma Patients With Mature, Autologous Monocyte-Derived Dendritic Cells Transfected With RNAs Encoding for Mage-3, MelanA, and Survivin Antigens|
- Safety and tolerability at every visit [ Designated as safety issue: Yes ]
- Overall survival as assessed by clinical staging (CT scan, positron emission tomography [PET]) every 3 months [ Designated as safety issue: No ]
- Time to progression as assessed by clinical staging (CT scan, PET) every 3 months [ Designated as safety issue: No ]
- Objective tumor response as assessed by clinical staging (CT scan, PET) every 3 months [ Designated as safety issue: No ]
- Duration of response as assessed by clinical staging (CT scan, PET) every 3 months [ Designated as safety issue: No ]
- Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit [ Designated as safety issue: No ]
|Study Start Date:||July 2003|
|Estimated Study Completion Date:||October 2014|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
- Determine the safety and tolerability of vaccination with autologous monocyte-derived dendritic cells (DC) transfected with RNAs encoding Melan-A, MAGE-3, and survivin antigens in patients with stage IV cutaneous melanoma.
- Determine whether tumor antigen-specific T-cell responses are induced in patients treated with this vaccine.
- Determine whether simultaneous loading of DC with keyhole limpet hemocyanin (KLH) significantly enhances induction of the Melan-A, MAGE-3, and survivin antigens in these patients.
- Determine clinical antitumor activity (e.g., objective tumor response, time to tumor progression, progression-free interval, and overall survival) in patients treated with this vaccine.
OUTLINE: This is an open-label, nonrandomized study.
- Phase I: Beginning 9-11 days before vaccination, patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are processed for the generation of dendritic cells (DC) to be used for vaccinations. PBMCs are transfected with RNAs encoding for Melan-A, MAGE-3, and survivin antigens. DC are pulsed with keyhole limpet hemocyanin (KLH) for some patients.
Patients receive antigen-pulsed (with or without KLH) DC vaccination subcutaneously (SC) on days 1, 15, 43, and 71 in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may proceed to the phase II portion of the study.
- Phase II: Patients undergo leukapheresis as in phase I on days 102, 354, and 690. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 127, 185, 269, 356, 521, and 692.
Patients are followed for 10 years.
PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00074230
|Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen|
|Erlangen, Germany, D-91052|
|Principal Investigator:||Gerold Schuler||Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen|