Messenger Ribonucleic Acid (mRNA) Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
|ClinicalTrials.gov Identifier: NCT00929019|
Recruitment Status : Terminated (slow accrual)
First Posted : June 26, 2009
Last Update Posted : December 8, 2016
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.
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.
This study is an open label non-randomized phase II intervention study.
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.
- 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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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).
- immunological response [ Time Frame: 2 years ]
- clinical response (progression free survival) [ Time Frame: 5 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00929019
|Radboud University Nijmegen Medical Centre|
|Nijmegen, Gelderland, Netherlands, 6500HB|
|The Rotterdam Eye Hospital|
|Rotterdam, Zuid-Holland, Netherlands, 3000LM|
|Principal Investigator:||Cornelis JA Punt, prof.MD||Radboud University Nijmegen Medical Centre, Dept of Medical Oncology|