Active Specific Intranodal Immunotherapy of Recombinant Vaccinia Virus in Locally Advanced to Metastatic Melanoma

December 1, 2009 updated by: University Hospital, Basel, Switzerland

Active Specific Intranodal Immunotherapy With a Recombinant Vaccinia Virus Expressing Three Melanoma Associated Epitopes and Two Costimulatory Molecules, Followed by Immunization With Synthetic Melanoma Associated Epitopes. A Phase I/II Trial in Patients With Stages IIb to IV Melanoma

The purpose of this study is to assess intranodal immunotherapy in locally advanced to metastatic melanoma patients (American Joint Committee on Cancer [AJCC] stages IIb to IV).

For this, the investigators capitalize on their previous melanoma clinical trial (published by Zajac P et al in Human Gene Ther 2003) and take advantage of a proprietary recombinant vaccinia virus (replication inactivated) expressing 5 minigenes: 3 melanoma associated antigens and 2 costimulatory molecules. Immunization with the recombinant vaccinia virus is followed by 3 boosts with soluble, synthetic melanoma associated antigens.

The patients are immunized intranodally (groin lymph node) under ultrasonographic guidance in an outpatient clinic. The protocol foresees 2 cycles of immunotherapy for alternate weeks and lasts 15 weeks.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators have conducted a phase I/II clinical trial based on the intradermal administration to stage III/IV melanoma patients of a recombinant vaccinia virus encoding tumor associated antigens and costimulatory epitopes for the priming of immune responses, followed by boosts with corresponding synthetic peptides (Zajac P et al in Human Gene Ther 2003). Specific cytotoxic T cells could be induced in a majority of patients following priming, but sustained responsiveness could not be maintained by peptide boosting on a long term basis. Emerging evidence supports the notion that expansion of specific T cells requires trafficking of antigen presenting cells loaded with specific determinants to lymphatic nodes, as induced, among others, by pro-inflammatory stimuli. Therefore, we now adopt the intranodal injection of the immunogenic formulations. As for the former melanoma active specific immunotherapy trial, GM-CSF is used as a supporting cytokine. The epitopes considered are expressed, either all or some of them, in over 90% of the melanomas in Western countries; namely, we immunize with Mart-1/Melan-A epitope 27-35, Gp-100 epitope 280-288 and tyrosinase epitope 1-9. As a consequence, HLA-A2 positivity is mandatory for inclusion in the trial. The 2 costimulatory molecules expressed by cells infected with our replication-incompetent recombinant vaccinia virus are B7.1 (CD80) and B7.2 (CD86).

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Basel, Switzerland, 4031
        • University Hospital Basel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Patients older than 18 years
  • Histologically proven melanoma in AJCC stages IIb to IV
  • Resected, recurrent or disseminated disease
  • HLA-A2.1 MHC phenotype
  • Karnofsky performance status equal or higher than 70%

Exclusion Criteria:

  • Patients younger than 18 years
  • Pregnancy or inability to perform anticonception
  • MHC phenotype other than HLA-A2.1
  • Other concurrent malignant disease
  • Estimated life expectancy of less than 6 months
  • Allergic skin diseases, including eczema, psoriasis and neurodermitis
  • Fever or active infection of the respiratory system
  • Concurrent severe cardiac or pulmonary disease (New York Heart Association [NYHA] III and IV)
  • Significant impairment of liver or kidney function (bilirubin > 30umol/l, GOT >2.5xN, GPT >2.5xN, alkaline phosphatase >2.5xN, creatinine >1.5xN adapted to the age)
  • Impairment of the immune system (leucocyte counts <3000/mm3 or granulocytes counts <1500/mm3)
  • Concurrent immunosuppressive therapy
  • Preexisting severe anemia (hemoglobin lower than 80 g/l)
  • Preexisting thrombocytopenia (platelet counts lower than 75,000/ul)
  • Ongoing chemotherapy or chemotherapy completed less than 6 weeks before enrollment in the trial
  • Any medical or psychiatric condition which, in the opinion of the treating physician or principal investigator, would unacceptably reduce the safety of the proposed treatment, would impair the delivery of treatment, or would preclude obtaining voluntary informed consent
  • Patients receiving any other concurrent investigational treatment, or any other concurrent treatment for their cancer
  • Patients who cannot avoid close contact with children less than 3 years of age or with immunocompromised household members

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety evaluation
Clinical response
Immune response assessment

Secondary Outcome Measures

Outcome Measure
Survival (disease-free survival [DFS], overall survival [OS])
Dose adaptation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Basel, Switzerland

Investigators

  • Principal Investigator: Michel Adamina, M.D., University Hospital, Basel, Switzerland
  • Study Chair: Daniel Oertli, M.D., University Hospital, Basel, Switzerland
  • Study Director: Michael Heberer, M.D., University Hospital, Basel, Switzerland
  • Principal Investigator: Giulio C Spagnoli, M.D., University Hospital, Basel, Switzerland
  • Principal Investigator: Walter R Marti, M.D., University Hospital, Basel, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2002

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

June 29, 2005

First Submitted That Met QC Criteria

June 29, 2005

First Posted (Estimate)

June 30, 2005

Study Record Updates

Last Update Posted (Estimate)

December 2, 2009

Last Update Submitted That Met QC Criteria

December 1, 2009

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GT1999017/05.050
  • SNF grant NPF 37 4037-55151

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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