Trial | NCT00929019  Report issue

Title

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

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Status

    Terminated

  • Study Participants

    23
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.

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.

Study design

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

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.

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 Started
Jun 30
2009
Primary Completion
Apr 30
2016
Study Completion
Apr 30
2016
Last Update
Dec 07
2018

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.

dendritic cell vaccination Experimental

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.

control arm No Intervention

For comparison, HLA-A2.1 negative patients will be monitored for clinical response (secondary endpoint).

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
No Results Posted