Melanoma Patients Immunized with Natural DenDritic Cells

This is a phase 3, randomized, double-blind, interventional study of nDC vaccination versus placebo. Dendritic cell-based immunotherapy consists of antigen-loaded autologous DC that are administered to patients with the intention of inducing antigen-specific T and B cell responses and proved safe with minimal side effects. Natural DC (nDC) consist of plasmacytoid DC and myeloid DC. Subjects will be randomized 2:1 and stratified by stage of disease, adjuvant radiotherapy, BRAF mutation status, HLA-type and nDC production centre. The treatment will be continued for a maximum of 1.5 years or until recurrence of disease, unacceptable toxicity or withdrawal from the study.

Eligibility Criteria:

• at least 18 years of age.
• Histologically confirmed stage III cutaneous melanoma, classified as IIIB or IIIC disease (AJCC 2009). Patients with completely resected in-transit and/or satellite metastases and patients with unknown primary melanoma are allowed in this trial.
• Radical lymph node dissection involved site with complete resection or sentinel node procedure (in case of patients without RLND because of limited sentinel-node positive disease) of melanoma as documented on the operating report and pathology report with at least the minimal levels excised as stated in national guidelines.
• Radical lymph node dissection involved site with complete resection or sentinel node procedure (in case of patients without RLND because of limited sentinel-node positive disease) must be performed within 12 weeks prior to start of study.
• Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
• Absence of distant metastases must be documented by a CT scan of the chest and abdomen (including pelvis) or a Positron Emission Tomography (PET) scan, the scan should have been performed within 6 weeks before surgery or after surgery prior to inclusion. In addition, a physical exam after surgery must be performed also excluding distant metastases.
• No clinical evidence for brain metastasis. If brain metastases are clinically suspected, a CT or Magnetic Resonance Imaging (MRI) scan of the brain must exclude brain metastases.
• World Health Organization (WHO) performance status of 0 or 1 at time of randomization.
• Adequate hematologic, renal and liver function as defined by laboratory values performed within 4 weeks of randomization.
• No second malignancy in the previous 5 years, with the exception of adequately treated carcinoma in-situ and basal or squamous cell carcinoma of the skin.
• No concomitant use of immunosuppressive drugs orally or intravenously. Topical and intranasal steroids are permitted.
• No uncontrolled infectious disease, i.e. negative testing for HIV, HBV, HCV and syphilis.
• No autoimmune disease such as, but not limited to, inflammatory bowel disease, multiple sclerosis, and lupus. Patients with type 1 diabetes mellitus, hypothyroidism after autoimmune thyroiditis and skin disorders are not excluded.
• No serious (bleeding and clotting) condition that may interfere with safe leukapheresis.
• No pregnant or lactating women.
• No Women Of Child-Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 8 weeks after the last administration of the treatment. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea > 12 consecutive months].
• Patients must have absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions must be discussed with the patient before registration in the trial.
• Expected adequacy of follow-up.
• Written informed consent.