myDC/pDC in Stage III Melanoma Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Myeloid and Plasmacytoid Blood Dendritic Cells for Immunotherapy of Stage III Melanoma Patients

Conditions
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Melanoma

Intervention / Treatment
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* Drug: A: myDC vaccination
* Drug: B: pDC vaccination
* Drug: C: combined myDC/pDC vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stage III melanoma WHO performance status 0-1 radical lymph node dissection is schedule or performed within 12 weeks prior to start of study treatment Exclusion Criteria: irresectable disease any concurrent adjuvant therapy concomitant use of oral immunosuppressive drugs autoimmune diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: myDC vaccination<br>intranodal injection with tumor peptide-loaded myeloid dendritic cells | Drug: A: myDC vaccination<br> <br> |
| Experimental: B: pDC vaccination<br>intranodal injection with tumor peptide-loaded plasmacytoid dendritic cells | Drug: B: pDC vaccination<br> <br> |
| Experimental: C: combined myDC/pDC vaccination<br>intranodal injection with tumor peptide-loaded myeloid and plasmacytoid dendritic cells | Drug: C: combined myDC/pDC vaccination<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 |