Immunization With 8 Peptides Mixed With Adjuvant Montanide ISA 51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma
The purposes of this study are to describe the immune response to individual peptides after immunization with a combination of 8 peptides and Montanide ISA-51; to determine the safety of this vaccine and; to document the tumor response to the vaccine.
Biological: 8 HLA-A2 restricted peptides and Montanide ISA-51
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Montanide ISA 51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma|
- - To describe the CTL response to individual peptides after immunization with a combination of 8 peptides and Montanide ISA-51.
- To determine the safety of immunization with combination of 8 peptides and Montanide ISA-51.
- To document the tumor response to immunization with a combination of 8 peptides and Montanide ISA-51.
- To obtain initial information on the relationship, if any, of T cell response patterns and tumor expression of the corresponding genes.
|Study Start Date:||January 2005|
|Estimated Study Completion Date:||December 2009|
|Estimated Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Patients will receive six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide, at 2-week intervals. The 8 peptides will be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously).
300 µg of each peptide will be mixed with 0.5ml of Montanide.
Tumor staging will be performed before inclusion and at week 13. PBL collections will be performed before starting the treatment, and at weeks 3, 7 and 13. They will provide the T lymphocytes for the immunological analysis.
At week 13, the PCR results of the pre-immune tumor biopsy must be available. Additional cycles of immunization, ONLY with the peptides expressed by the tumor, mixed with Montanide, will be proposed to patients without tumor progression requiring another treatment. A second cycle of 3 injections at 6-week intervals will be started at week 17, followed by a third cycle of 12 injections at 3-month intervals, starting at month 11. At any time, progression of the disease necessitating any treatment not allowed during the study, will result in withdrawal.
The immune response may well be a limiting factor to the therapeutic efficacy of the vaccine. If this is the case, it then becomes crucial to understand why some patients develop a cytolytic T lymphocyte (CTL) response against the vaccine, while the majority of them does not so. One possible explanation for the low frequency of clinical responses is that each injection of a single peptide has a low probability to provide the adequate stimulus to activate very rare CTL precursors. This probability should be increased if several peptides known to be undoubtedly associated with tumor regressions were used together to immunize patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00145158
|Clinique Universitaires St-Luc|
|Brussels, Belgium, B-1200|
|Ludwig Institute for Cancer Research|
|Brussels, Belgium, B-1200|
|Study Chair:||Nicolas VanBaren, MD||Ludwig Institute for Cancer Research|
|Study Director:||Thierry BOON, PhD||Ludwig Institute for Cancer Research|