Dendritic Cell Vaccination in Melanoma Patients Scheduled for Regional Lymph Node Dissection

February 18, 2009 updated by: Radboud University Medical Center

Active Immunization of Patients With Stage III and IV Melanoma in Whom a Regional Lymph Node Dissection is Planned, With Peptide-Pulsed Dendritic Cells: Evaluation of in Vivo Immune and Clinical Response and Migration

Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients, and both immunological and clinical responses have been observed. For these therapies accurate delivery to target organs is essential. Correct delivery and subsequent migration of vaccinated DCs to regional lymph nodes is of paramount importance for effective stimulation of the immune system. Currently it is not known what the best route of administration is for DC vaccines.

Using magnetically labeled DCs, we investigate the potential of MRI cell tracking to monitor DC therapy. This is investigated in stage III/IV melanoma patients in whom a regional lymph node dissection is scheduled. Autologous monocyte-derived DCs are labeled with the clinically approved superparamagnetic iron oxide (SPIO) formulation Endorem and 111In-oxine and injected either in the skin or directly in lymph nodes under ultrasound guidance. Two days after vaccination patients are monitored with scintigraphy and MR imaging. Lymph nodes are then resected. Subsequently patients receive 3 more vaccination with DCs. During and after therapy immune responses against the used melanoma peptides are monitored.

Study Overview

Status

Completed

Conditions

Melanoma Stage III or IV

Intervention / Treatment

Biological: Peptide-pulsed dendritic cells

Study Type

Interventional

Enrollment (Anticipated)

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
- PO Box 9101
  - Nijmegen, PO Box 9101, Netherlands, 6500 HB
    - Radboud University Nijmegen Medical Centre

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

Genders Eligible for Study

All

Description

Inclusion criteria:

Histologically documented evidence of melanoma

Stage III-IV melanoma according to the 2001 AJCC criteria

Radical lymph node dissection planned, either with curative (stage III) or palliative (stage IV) intent

Melanoma expressing gp100 (compulsory) and tyrosinase (non-compulsory)

HLA-A2.1 phenotype according to lymphocyte HLA typing

ECOG performance status 0-1, life expectancy > 3 months

Age 18-75 years

Interval since last prior chemotherapy, immunotherapy or radiotherapy at least 4 weeks, no residual toxicity of prior treatment.

WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l

Written informed consent

Expected adequacy of follow-up

Exclusion criteria:

No clinical signs of CNS metastases, in patients with a clinical suspicion of other metastases diagnostic tests should be performed to exclude this.

No concomitant use of corticosteroids or other immunosuppressive agents

No history of second malignancy within the last 5 years. Adequately treated basal carcinoma of skin or carcinoma in situ of cervix is acceptable within this period

No serious concomitant disease, no active infections. No autoimmune disease or organ allografts, no clinical suspicion of HIV or Hepatitis B

No contra-indications for MRI-scanning: claustrophobia, pacemaker or pacemaker threads, cerebral clips or artificial heartvalves, internal hearing prosthesis No known allergy to shell fish (contains KLH)

No pregnant or lactating women

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Immune response Time Frame: during the first 10 years	during the first 10 years
Migration efficacy Time Frame: during the first 1-2 years	during the first 1-2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical response Time Frame: during the first 10 years	during the first 10 years

Collaborators and Investigators

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

Sponsor

Radboud University Medical Center

Collaborators

Dutch Cancer Society

Investigators

Principal Investigator: Prof. C.J.A. Punt, MD, PhD, Radboud University Medical Center
Principal Investigator: Prof. C.G. Figdor, PhD, Radboud University Medical Center

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.

General Publications

Helpful Links

Home page of the Radboud University Nijmegen Medical Centre

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

September 1, 1999

Primary Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

October 21, 2005

First Submitted That Met QC Criteria