NCT00145158

Immunization With 8 Peptides Mixed With CpG 7909 or Montanide ISA51 in Patients With Metastatic Cutaneous Melanoma

Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Adjuvant CpG 7909 or Montanide ISA51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purposes of this study are to describe the immune response to individual peptides after immunization with a combination of 8 peptides and CpG 7909 or Montanide ISA51; to determine the safety of the vaccines and; to document the tumor response in patients receiving the vaccines.

Detailed description

Patients received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with either CpG 7909 or Montanide ISA51, at 2-week intervals. The 8 peptides were 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 (except MAGE-10.A2 150 µg) was mixed with 4 mg CpG 7909 (Cohort 1) or 0.5ml of Montanide ISA51 (Cohort 2). In Cohort 2, the Tyrosinase.A2 was administered without Montanide ISA51. Tumor staging was performed before inclusion and at week 13. Peripheral Blood Lymphocytes (PBL) collections were performed before starting the treatment, and at weeks 3, 7 and 13. They provided 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 ISA51, 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 cytotoxic t-lymphocyte (CTL) response against the vaccine, while the majority of them do not. 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.

Conditions

• Malignant Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	8 HLA-A2-restricted peptides and Montanide ISA51
BIOLOGICAL	8 HLA-A2-restricted peptides and CpG 7909

Timeline

• Start date: 2005-01-01
• Primary completion: 2007-11-30
• Completion: 2009-03-12
• First posted: 2005-09-05
• Last updated: 2022-10-10
• Results posted: 2022-04-07

Locations

2 sites across 1 country: Belgium