Immunotherapy of HLA-A2 Positive Stage III/IV Melanoma Patients

Immunotherapy of HLA-A2 Positive Stage III/IV Melanoma Patients With CpG7909, Tumor Antigenic Peptides and Montanide

The purpose of this study is to determine whether vaccination with tumor antigenic peptides and both CpG and Montanide adjuvants can induce an immune response in melanoma patients and to assess the safety of this vaccination.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: group 1; Biological: group 2; Biological: group 3; Biological: group 4

Detailed Description

Immune therapy with tumor antigenic peptides is generally quite well tolerated. However, immune activation is often only weak or even undetectable, and clinical responses (supposedly corresponding to protective immunity) are unfortunately infrequent. Further progress is required to improve the vaccines, with the goal to increase the strength of immune activation.

The tumor antigenic peptides Melan-A/Mart-1 (EAA and ELA) and Tyrosinase (YMD) are combined with two drugs in this study, both of which are known to enhance immune responses: first, CpG 7909 oligodeoxynucleotides, and second, Montanide ISA-51.

• Group 1: vaccination with Melan-A analog peptide + CpG and Montanide adjuvants;
• Group 2: vaccination with Melan-A natural peptide + CpG and Montanide adjuvants;
• Group 3 : vaccination with Melan-A natural and Tyrosinase peptides + CpG and Montanide adjuvants;
• Group 4 : vaccination with Melan-A analog and Tyrosinase peptides + CpG and Montanide adjuvants.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Ludwig Institute for Cancer Research + Multidisciplinary Oncology Center at the Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed stage III or stage IV melanoma
• Tumor expression of Melan-A +/- Tyrosinase
• Human leukocyte antigen-A2 (HLA-A2) positive

Exclusion Criteria:

• Clinically significant heart disease
• Serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders or uncontrolled peptic ulcer, or seizure or central nervous system disorders
• History of immunodeficiency disease or autoimmune disease
• Coagulation or bleeding disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1; Melan-A analog peptide + CpG + Montanide	Biological: group 1; Melan-A analog peptide + CpG + Montanide
Experimental: group 2; Melan-A natural peptide + CpG + Montanide	Biological: group 2; Melan-A natural peptide + CpG + Montanide
Experimental: group 3; Melan-A natural peptide + Tyrosinase YMD peptide + CpG + Montanide	Biological: group 3; Melan-A natural peptide + Tyrosinase YMD peptide + CpG + Montanide
Experimental: group 4; Melan-A analog peptide + Tyrosinase YMD peptide + CpG + Montanide	Biological: group 4; Melan-A analog peptide + Tyrosinase YMD peptide + CpG + Montanide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Melan-A and Tyrosinase specific CD8+ T-cell reactivity will be measured by Tetramers and Elispot assays	Change from baseline in CD8 T-cells reactivity at day 375
Safety of vaccination will be assessed according to National Cancer Institute Common Toxicity Criteria (NCI CTC) scale	Change from baseline to day 375

Secondary Outcome Measures

Outcome Measure	Time Frame
In patients with measurable disease, tumor response will be assessed radiologically	Change from baseline in tumor response at day 375

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: Ludwig Institute for Cancer Research
• Investigators: Principal Investigator: Olivier Michielin, MD, Ludwig Institute for Cancer Research

Publications and helpful links

General Publications

• Speiser DE, Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini JC, Romero P. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest. 2005 Mar;115(3):739-46. doi: 10.1172/JCI23373.
• Baumgaertner P, Jandus C, Rivals JP, Derre L, Lovgren T, Baitsch L, Guillaume P, Luescher IF, Berthod G, Matter M, Rufer N, Michielin O, Speiser DE. Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells. Int J Cancer. 2012 Jun 1;130(11):2607-17. doi: 10.1002/ijc.26297. Epub 2011 Aug 24.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 31, 2005
• First Submitted That Met QC Criteria: May 31, 2005
• First Posted (Estimate): June 1, 2005

Study Record Updates

• Last Update Posted (Estimate): April 22, 2013
• Last Update Submitted That Met QC Criteria: April 19, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Immunotherapy; Melanoma; Vaccination; CpG; Melan-A/Mart-1 peptide; Montanide; Tyrosinase peptide
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: LUD 2000-018