Melanoma Stage III or IV Clinical Trial
Official title:
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.
| Status | Completed |
| Enrollment | 40 |
| Est. completion date | |
| Est. primary completion date | January 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 75 Years |
| Eligibility |
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 |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Radboud University Nijmegen Medical Centre | Nijmegen | PO Box 9101 |
| Lead Sponsor | Collaborator |
|---|---|
| Radboud University | Dutch Cancer Society |
Netherlands,
Adema GJ, de Vries IJ, Punt CJ, Figdor CG. Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol. 2005 Apr;17(2):170-4. Review. — View Citation
de Vries IJ, Bernsen MR, Lesterhuis WJ, Scharenborg NM, Strijk SP, Gerritsen MJ, Ruiter DJ, Figdor CG, Punt CJ, Adema GJ. Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol. 2005 Aug 20;23(24):5779-87. — View Citation
de Vries IJ, Eggert AA, Scharenborg NM, Vissers JL, Lesterhuis WJ, Boerman OC, Punt CJ, Adema GJ, Figdor CG. Phenotypical and functional characterization of clinical grade dendritic cells. J Immunother. 2002 Sep-Oct;25(5):429-38. — View Citation
De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, Adema GJ, Punt CJ, Figdor CG. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res. 2003 Jan 1;63(1):12-7. — View Citation
de Vries IJ, Lesterhuis WJ, Barentsz JO, Verdijk P, van Krieken JH, Boerman OC, Oyen WJ, Bonenkamp JJ, Boezeman JB, Adema GJ, Bulte JW, Scheenen TW, Punt CJ, Heerschap A, Figdor CG. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol. 2005 Nov;23(11):1407-13. Epub 2005 Oct 30. — View Citation
de Vries IJ, Lesterhuis WJ, Scharenborg NM, Engelen LP, Ruiter DJ, Gerritsen MJ, Croockewit S, Britten CM, Torensma R, Adema GJ, Figdor CG, Punt CJ. Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res. 2003 Nov 1;9(14):5091-100. — View Citation
Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. Review. — View Citation
Lesterhuis WJ, de Vries IJ, Adema GJ, Punt CJ. Dendritic cell-based vaccines in cancer immunotherapy: an update on clinical and immunological results. Ann Oncol. 2004;15 Suppl 4:iv145-51. Review. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Immune response | during the first 10 years | No | |
| Primary | Migration efficacy | during the first 1-2 years | No | |
| Secondary | Clinical response | during the first 10 years | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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