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

December 5, 2018 updated by: Radboud University Medical Center

mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients

  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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500HB
        • Radboud University Nijmegen Medical Centre
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3000LM
        • The Rotterdam Eye Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
immunological response
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
clinical response (progression free survival)
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Rotterdam Eye Hospital

Investigators

  • Principal Investigator: Cornelis JA Punt, prof.MD, Radboud University Nijmegen Medical Centre, Dept of Medical Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

June 25, 2009

First Submitted That Met QC Criteria

June 25, 2009

First Posted (Estimate)

June 26, 2009

Study Record Updates

Last Update Posted (Actual)

December 7, 2018

Last Update Submitted That Met QC Criteria

December 5, 2018

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL22553.000.08
  • KUN2008-035

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Uveal Melanoma

Clinical Trials on autologous dendritic cells electroporated with mRNA

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in China

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe