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Messenger Ribonucleic Acid (mRNA) Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients

This study is currently recruiting participants.
Verified November 2012 by Radboud University
Sponsor:
Collaborator:
Oogziekenhuis Rotterdam, Rotterdam Eye Hospital
Information provided by (Responsible Party):
Prof. Dr. Winette van der Graaf, Radboud University
ClinicalTrials.gov Identifier:
NCT00929019
First received: June 25, 2009
Last updated: November 29, 2012
Last verified: November 2012
History of Changes
  Purpose

  1. Rationale

    Immunotherapy applying ex vivo generated and tumor antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Most of the successful results have been observed in patients with minimal residual disease, rather than patients with advanced metastatic disease. Moreover, the investigators' preliminary results show that presence of tumor epitope specific T cells in biopsies taken from delayed type hypersensitivity (DTH) reaction sites highly correlates with prolonged progression free survival (PFS).

    Within uveal melanoma patients, a group with high risk of metastatic disease can be identified on basis of tumor specific genetic changes in loss of chromosome 3.

    At present no standard adjuvant or systemic treatment is available. Applying DC-based immunotherapy in this group of high risk patients might reduce the risk of recurrence without interference in the current treatment guidelines.

  2. Objectives

    In this joint clinical study of Radboud University Nijmegen Medical Centre (RUNMC) and Rotterdam Eye Hospital, the investigators aim to determine the in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC.

  3. Study design

    This study is an open label non-randomized phase II intervention study.

  4. Study population

    The investigators' study population consists of HLA-A2 positive patients with a high risk uveal melanoma with proven expression of melanoma associated antigens tyrosinase and/or gp100.

  5. Main study endpoints

This is an exploratory study aiming to demonstrate proof of principle. The first study endpoints are in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC, administered i.v./i.d. and toxicity. Secondary study endpoints are progression free survival, overall survival, and toxicity.


Condition Intervention Phase
Uveal Melanoma
 Biological: autologous dendritic cells electroporated with mRNA
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma
U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • immunological response [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • clinical response (progression free survival) [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dendritic cell vaccination
HLA-A2.1 positive patient will receive 3 biweekly intradermal/intravenous vaccination with autologous mRNA transfected mature dendritic cells, followed by a DTH skin test for monitoring purposes. One such cycle is repeated every 6 months if no signs of progression, up to a total of 3 cycles.
 Biological: autologous dendritic cells electroporated with mRNA
Autologous mature monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase are vaccinated intradermal/intravenously 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations.
No Intervention: control arm
For comparison, HLA-A2.1 negative patients will be monitored for clinical response (secondary endpoint).

  Eligibility

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

Inclusion Criteria:

  • histological documented uveal melanoma
  • HLA-A2.1 phenotype (intervention arm)
  • non-HLA-A2.1 phenotype (control arm)
  • melanoma expressing gp100 and/or tyrosinase
  • high risk genetic profile (loss of chromosome 3) determined by FISH
  • interval since local treatment of uveal melanoma < 12 months
  • no signs of liver metastasis determined by diagnostic CT-abdomen
  • normal serum LDH
  • no signs of cerebral metastases
  • bilirubin < 25 micromol/l
  • WHO performance scale 0-1
  • age 18-75 years
  • written informed consent
  • expected adequacy of followup
  • no pregnant or lactating women

Exclusion Criteria:

  • history of second malignancy, except adequately treated basal cell carcinoma
  • serious active infections
  • autoimmune disease or organ allografts
  • concomitant use of immunosuppressive drugs
  • known allergy to shell-fish
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00929019

Contacts
Contact: Don Paridaens, MD +31 10 401 7777 d.paridaens@oogziekenhuis.nl
Contact: Cornelis JA Punt, prof. MD +31 24 361 0353 C.Punt@onco.umcn.nl

Locations
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Gelderland, Netherlands, 6500HB
Contact: Cornelis JA Punt, prof.MD     +31 24 361 0353     C.Punt@onco.umcn.nl    
Principal Investigator: Cornelis JA Punt, prof. MD            
The Rotterdam Eye Hospital Recruiting
Rotterdam, Zuid-Holland, Netherlands, 3000LM
Contact: Don Paridaens, MD     +31 10 401 7777     d.paridaens@oogziekenhuis.nl    
Principal Investigator: Don Paridaens, MD            
Sponsors and Collaborators
Radboud University
Oogziekenhuis Rotterdam, Rotterdam Eye Hospital
Investigators
Principal Investigator: Cornelis JA Punt, prof.MD Radboud University Nijmegen Medical Centre, Dept of Medical Oncology
  More Information

Additional Information:
Radboud University Nijmegen Medical Centre  This link exits the ClinicalTrials.gov site
Rotterdam Eye Hospital  This link exits the ClinicalTrials.gov site
Nijmegen Centre for Molecular Life Sciences  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Prof. Dr. Winette van der Graaf, professor, Radboud University
ClinicalTrials.gov Identifier: NCT00929019     History of Changes
Other Study ID Numbers: NL22553.000.08, KUN2008-035
Study First Received: June 25, 2009
Last Updated: November 29, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
uveal melanoma
chromosome 3
high risk
immunotherapy
 adjuvant
high risk genetic profile
loss of chromosome 3

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

ClinicalTrials.gov processed this record on June 18, 2013