Trial of Vaccine Therapy With mRNA- Transfected Dendritic Cells in Patients With Advanced Malignant Melanoma

Phase I/II Trial of Vaccine Therapy With mRNA- Transfected Dendritic Cells in Patients With Advanced Malignant Melanoma

PRIMARY OBJECTIVES: Determination of safety and toxicity of vaccination with patients' tumour mRNA transfected DCs .

SECONDARY OBJECTIVES:Determine immunological response to the vaccine (induction of specific T-cell response) and assessment of tumour response

Inclusion Criteria:

• Accessible tumour tissue for vaccine production (extraction of tumour mRNA) i.e.subcutaneous or lymph node metastases.
• Must be at least 18 years of age.
• Must have histologically confirmed advanced, metastatic cutaneous melanoma no longer amenable for surgery.
• Must have evidence of disease progression and measurable or evaluable metastases
• Must be ambulatory with a ECOG performance score of <2
• Must have lab.values as following :

ANC > 1.5 x 109/L; platelets > 100 x 109/L, Hb > 9g/dL (> 5.6 mmol/L). Creatinine < 140 µmol/L (1.6 mg/dL); if borderline, the creatinine clearance > 40 mL/min, Bilirubin < 20% above the upper limit of normal, ASAT and ALAT < 2.5 the upper limit of normal. Albumin > 2.5 g/L.

• Prior radiotherapy: A minimum of 4 weeks (8 weeks in case of extensive radiotherapy) must have elapsed between the end of the prior radiotherapy and entry into the protocol.
• Prior chemotherapy: A minimum 4 weeks must have elapsed between the end of the prior chemotherapy and entry into the protocol.
• Signed informed consent of the patients for the treatment and follow up must be obtained and documented according to the ICH-GCP Guidelines.

Exclusion Criteria:

• History of prior malignancy other than melanoma, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin and ca. cervix stage 1B.
• Active infection requiring antibiotic therapy.
• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia.
• Autoimmune disease currently treated with steroids.
• Adverse reactions to vaccines such as anaphylaxis or other serious reactions.
• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome.
• Chemotherapy or other potentially immune-suppressive therapy that has been administered within 4 weeks prior to vaccination.
• Pregnancy or lactation.
• Any reason why, in the opinion of the investigator, the patient should not participate.