Melanoma Stage III or IV
Conditions
Keywords
Dendritic cells, Immunotherapy, Vaccination, Melanoma, Peptides, MRI, Scintigraphy, Immune response
Brief summary
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.
Interventions
BIOLOGICALPeptide-pulsed dendritic cells
peptide-pulsed dendritic cells
Sponsors
Dutch Cancer Society
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immune response | during the first 10 years |
| Migration efficacy | during the first 1-2 years |
Secondary
| Measure | Time frame |
|---|---|
| Clinical response | during the first 10 years |
Countries
Netherlands
Outcome results
None listed