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

Study Overview
=================
Brief Summary
-----------------
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

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

Conditions
-----------------
Malignant Melanoma

Intervention / Treatment
-----------------
* Biological: Dendritic Cells (DC) malignant melanoma
* Procedure: IL-2


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dendritic Cells (DC) malignant melanoma<br>22 patients were included in this arm. | Biological: Dendritic Cells (DC) malignant melanoma<br>* The patients were assigned to intradermal or intranodal DC vaccination<br>|
| Experimental: DC vaccine plus IL-2<br>To improve the efficacy of the DC vaccine, IL-2 was administrated at the vaccination site through direct lymph node injection. 9 patients were included in this arm. | Biological: Dendritic Cells (DC) malignant melanoma<br>* The patients were assigned to intradermal or intranodal DC vaccination<br>Procedure: IL-2<br>* IL-2 were administrated by intranodal injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of safety and toxicity of vaccination with patients' tumour mRNA transfected DCs | Biochemistry and hematology results, vital signs and ECOG performance status are measured at those timepoints. | Patients are coming every week during 6 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine immunological response to the vaccine (induction of specific T-cell response) |  | 6 weeks and 3 months after study start | 
| Assessment of tumour response. | CT-scan | 3 months after study start |