mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma

Exclusion Criteria

• •4. baseline tumor assessment by whole-body FDG-PET/CT, patients should be free from measurable tumor lesions (RECIST (v1.1)), and free from symptomatic non-measurable tumor lesions
• •5. Prior local treatment of primary and metastatic tumor lesions is allowed . Treated tumor lesions should be free from progression at baseline assessment
• •6. Normal organ function and normal hematological parameters;laboratory parameters should be within normal range, except following laboratory parameters:HEMOGLOBIN ≥ 10 G/DL; GRANULOCYTES ≥ 1,500/µL; LYMPHOCYTES ≥ 1000/µL; PLATELETS ≥ 100,000/µL; SERUM CREATININ ≤ 2.0 MG/DL; SERUM BILIRUBIN ≤ 2.0 MG/DL; AST AND ALT ≤ 2 X THE NORMAL UPPER LIMITS; LDH ≤ 1,5X NORMAL UPPER LIMIT; CRP ≤ 1,5X NORMAL UPPER LIMIT; PROTHROMBIN TIME (PT) INTERNATIONAL NORMALIZED RATIO (INR) AND PARTIAL THROMBOPLASTIN TIME (PTT) WITHIN NORMAL LIMITS
• •7. Negative serology for HCV, and HIV; absence of active infection with HBV, and Syphilis; If positive results for HepB or Syphilis indicate immunity and are not indicative of active infection, the patient can enter the study.
• •8. Adequate venous access(to undergo leukapheresis)
• •9. No prior systemic therapy for melanoma
• •10. Full recovery from all prior therapies. A period of 4 weeks following major surgery, radiation therapy, or ILP, or any other major invasive procedure is required
• •11. Baseline WHO performance status of 0 or 1
• •12. Male and female patients ≥ 18 years
• •13. No need for uninterrupted therapeutic anticoagulation
• •14. No prior history of a serious autoimmune disorder
• •15. No concomitant medication with immune suppressive drugs
• •16. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized.
• •1. Evidence of immunodeficiency or autoimmune disease requiring medical treatment (e.g. corticosteroids or other immunosuppressive drugs).Vitiligo is not an exclusion criterion
• •2. Any serious acute or chronic illnesses (e.g. heart disease NYHA Class III or IV,renal-,liver- or pulmonary insufficiency) or other conditions requiring concurrent medications not allowed during this study (e.g. active chronic infections requiring antibiotics)
• •3. History of malignancy. Curatively treated cervical carcinoma in situ,or squamous-,or basal cell carcinoma of the skin, or subjects who have been treated and recurrence-free of other malignancies for more than 5 years following the diagnosis are eligible
• •4. Inability to undergo FDG-PET/CT, or MRI examination
• •5. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
• •6. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment
• •7. Subject is pregnant (positive serum beta-HCG test at screening) or is currently breast-feeding, anticipates becoming pregnant/impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment
• •8. Current alcohol dependence or drug abuse
• •9. Known hypersensitivity to the study treatment
• •10. Legal incapacity or limited legal capacity
• •11. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• •12. Signs and symptoms suggestive of transmissible spongiform encephalopathy,or family members who suffer(ed) from such.