Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

September 28, 2009 updated by: Radboud University Medical Center

In Vivo Responses of DC Vaccines Presenting HLA Class I and II Restricted Tumor Epitopes Either by Peptide-pulsing or mRNA Transfection in Melanoma Patients

Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

64

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

  • Netherlands
    • PO Box 9101
      • Nijmegen, PO Box 9101, Netherlands, 6500 HB
        • Radboud University Nijmegen Medical Center

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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

For both stage III and IV

  • Histological proof of cutaneous melanoma
  • Melanoma expressing both gp100 and tyrosinase, each in approximately 20% or more of cells by immunohistochemistry staining,
  • HLA type A2 and/or A3, with known HLA-DR4 expression,
  • WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l.
  • Expected adequacy of follow-up,
  • Written informed consent.

For Stage III only

  • Stage III melanoma according to the 2001 AJCC criteria.
  • Start of treatment within 2 months of lymph node dissection for melanoma stage III

For stage IV only

-Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal

Exclusion Criteria:

For both stage III and IV

  • No autoimmune disorders, no concomitant use of immunosuppressive drugs,
  • no serious concomitant disease, no serious active infections, no other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin,
  • No known allergy to shell fish (contains KLH) are excluded.
  • No pregnancy or lactation,

For stage III only:

  • No signs or symptoms of distant metastases as defined by normal history, physical examination, chest X-ray and serum LDH.
  • No concomitant or previous systemic treatment for melanoma

For stage IV only:

  • No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this.
  • No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: MHC Class I restricted epitopes
HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase
Biological: autologous dendritic cell vaccine
Experimental: MHC Class I and II restricted epitopes
HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase
Biological: autologous dendritic cell vaccine
Experimental: mRNA transfected DC
HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase
Biological: autologous dendritic cell vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Immune response
Time Frame: first 10 years
first 10 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety
Time Frame: first 10 years
first 10 years

Collaborators and Investigators

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

Sponsor

Radboud University Medical Center

Collaborators

Dutch Cancer Society

Investigators

  • Principal Investigator: Prof. C.J.A. Punt, MD, PhD, Radboud University Nijmegen Medical Center
  • Principal Investigator: Prof. G.J. Adema, PhD, Radboud University Nijmegen Medical Center/Nijmegen Center for Molecular Life Sciences

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

April 1, 2004

Primary Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

October 21, 2005

First Submitted That Met QC Criteria

October 21, 2005

First Posted (Estimate)

October 24, 2005

Study Record Updates

Last Update Posted (Estimate)

September 29, 2009

Last Update Submitted That Met QC Criteria

September 28, 2009

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2003-2917
  • KWF 2003-2917

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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