Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00929019
Recruitment Status : Terminated (slow accrual)
First Posted : June 26, 2009
Last Update Posted : December 7, 2018
Rotterdam Eye Hospital
Information provided by (Responsible Party):
Radboud University

Brief Summary:
  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 or disease Intervention/treatment Phase
Uveal Melanoma Biological: autologous dendritic cells electroporated with mRNA Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
Study Start Date : June 2009
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Arm Intervention/treatment
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).

Primary Outcome Measures :
  1. immunological response [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. clinical response (progression free survival) [ Time Frame: 5 years ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00929019

Layout table for location information
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500HB
The Rotterdam Eye Hospital
Rotterdam, Zuid-Holland, Netherlands, 3000LM
Sponsors and Collaborators
Radboud University
Rotterdam Eye Hospital
Layout table for investigator information
Principal Investigator: Cornelis JA Punt, prof.MD Radboud University Nijmegen Medical Centre, Dept of Medical Oncology
Additional Information:
Layout table for additonal information
Responsible Party: Radboud University Identifier: NCT00929019    
Other Study ID Numbers: NL22553.000.08
First Posted: June 26, 2009    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: September 2015
Keywords provided by Radboud University:
uveal melanoma
chromosome 3
high risk
high risk genetic profile
loss of chromosome 3
Additional relevant MeSH terms:
Layout table for MeSH terms
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases