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

This study has been completed.
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00243529
First received: October 21, 2005
Last updated: September 28, 2009
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
Melanoma Stage III or IV
Biological: autologous dendritic cell vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Immune response [ Time Frame: first 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Time Frame: first 10 years ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: April 2004
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00243529

Locations
Netherlands
Radboud University Nijmegen Medical Center
Nijmegen, PO Box 9101, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
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
  More Information

Additional Information:
Publications:

Responsible Party: Prof. C.J.A. Punt, MD, PhD, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT00243529     History of Changes
Other Study ID Numbers: 2003-2917, KWF 2003-2917
Study First Received: October 21, 2005
Last Updated: September 28, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Dendritic cells
Melanoma
Vaccine
Immunotherapy
RNA
Peptides

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 16, 2014