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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Melanoma

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Trial Information

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 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).


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety evaluation

Principal Investigator

Michel Adamina, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital, Basel, Switzerland

Authority:

Switzerland: Swissmedic

Study ID:

GT1999017/05.050

NCT ID:

NCT00116597

Start Date:

November 2002

Completion Date:

December 2008

Related Keywords:

  • Melanoma
  • Active Specific Immunotherapy
  • Intranodal
  • Cancer
  • Melanoma stages IIb to IV
  • Gene Therapy
  • Recombinant Vaccinia virus
  • HLA-A2
  • Mart-1/Melan-A, Gp-100, tyrosinase
  • Clinical Trial
  • Phase I/II
  • Melanoma
  • Vaccinia

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