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This is an interventional study to test the immunogenicity of combined adjuvant myDC and pDC vaccination versus adjuvant myDC or pDC vaccination alone in stage III melanoma patients.
Stage lll melanoma patients will receive pDC (arm A, n=10), myDC (arm B, n=10) or combined pDC/myDC (arm C, n=10). Subsequent vaccinations will be performed according to the protocol: 2 biweekly vaccinations of intranodal injections with pDC, myDC or the combination with pDC and myDC. After each vaccination the investigators will examine peripheral blood for proliferative and humoral KLH immune responses. After the vaccinations, a DTH with peptide loaded blood DC is performed from which biopsies are taken for T cell analysis. lf patients remain disease free, the investigators will repeat this cycle with a 6 months interval up to a total of three cycles. lf a tumor recurrence occurs a biopsy will be taken for laboratory evaluation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A: myDC vaccination | Experimental | intranodal injection with tumor peptide-loaded myeloid dendritic cells |
|
| B: pDC vaccination | Experimental | intranodal injection with tumor peptide-loaded plasmacytoid dendritic cells |
|
| C: combined myDC/pDC vaccination | Experimental | intranodal injection with tumor peptide-loaded myeloid and plasmacytoid dendritic cells |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| A: myDC vaccination | Drug |
| ||
| B: pDC vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| immunogenicity - type I IFN | Type I IFN gene expression in PBMC shortly after vaccination. The occurrence of the type I IFN response in patients will be compared between the arms. | up to 1.5 years |
| immunogenicity - response to KLH | Proliferative, effector cytokine and humoral responses to keyhole limpet hemocyanin (KLH).The occurrence of the response will be compared between the arms. | up to 1.5 years |
| immunogenicity - T cells in DTH | Functional response and tetramer analysis of DTH infiltrating T cells against tumor peptides. The occurrence of the response will be compared between the arms. | up to 1.5 years |
| Measure | Description | Time Frame |
|---|---|---|
| biodistribution/localization of pDC and myDC in the lymph node | biodistribution/localization of the injected labeled pDC and/or myDC in the resected lymph node by multiple techniques | within 1 week after vaccination 1 |
| safety - Toxicity will be assessed according to the NCI Common Toxicity Criteria, CTC version 4.0 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Winald Gerritsen | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Nijmegen Medical Centre | Nijmegen | 6500 HB | Netherlands |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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|
| C: combined myDC/pDC vaccination | Drug |
|
Toxicity will be assessed according to the NCI Common Toxicity Criteria, CTC version 4.0 |
| up to 1.5 years |
| quality of life | To assess the quality of life the EORTC QLQ-C30 questionnaire will be used. | 5 years |
| progression-free survival | time from radical lymph node dissection to recurrence of (distant) disease | 5 years |
| overall survival | time from radical lymph node dissection to death | 5 years |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |