Brief Title
Messenger Ribonucleic Acid (mRNA) Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
Official Title
mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
immunological response
Secondary Outcome
clinical response (progression free survival)
Condition
Uveal Melanoma
Intervention
autologous dendritic cells electroporated with mRNA
Study Arms / Comparison Groups
dendritic cell vaccination
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
23
Start Date
June 2009
Completion Date
April 2016
Primary Completion Date
April 2016
Eligibility 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
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Cornelis JA Punt, prof.MD, ,
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT00929019
Organization ID
NL22553.000.08
Secondary IDs
KUN2008-035
Responsible Party
Sponsor
Study Sponsor
Radboud University Medical Center
Collaborators
Rotterdam Eye Hospital
Study Sponsor
Cornelis JA Punt, prof.MD, Principal Investigator, Radboud University Nijmegen Medical Centre, Dept of Medical Oncology
Verification Date
September 2015