Single-step antigen loading and TLR activation of dendritic cells by mRNA electroporation for vaccination in stage III and IV melanoma patients

Completed

Conditions: malignant melanoma
10040900

Registration Number: NL-OMON32492

Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 28

Inclusion Criteria

All patients:
- histologically documented evidence of melanoma
- stage III or IV melanoma according to the 2001 AJCC criteria
- melanoma expressing gp100 (compulsory) and tyrosinase (non-compulsory)
- WHO performance status 0-1 (Karnofsky 100-70)
- life expectancy >3 months
- age 18-70 years
- no clinical signs or symptoms of CNS metastases
- WBC >3.0×109/l, lymphocytes >0.8×109/l, platelets >100×109/l,
serum creatinine <150 µmol/l, serum bilirubin <25 µmol/l
- normal serum LDH (<=450 U/l)
- expected adequacy of follow-up
- no pregnant or lactating women
- written informed consent
and in addition:
Stage III melanoma
- interval since radical regional lymphnode dissection is <2 months
Stage IV melanoma
- at least one unidimensional measurable target lesions according to RECIST, not previously irradiated, and no significant symptoms of disease requiring other palliative treatments

Exclusion Criteria

- prior chemotherapy, immunotherapy or radiotherapy <4 weeks prior to planned
vaccination or presence of treatment-related toxicity
- history of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
- serious active infections, HbsAg or HIV positive or autoimmune diseases or
organ allografts
- concomitant use of immunosuppressive drugs
- known allergy to shell fish (since it contains KLH)
- rapidly progressive disease
- any serious clinical condition that may interfere with the safe administration of DC

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objectives of the study are to investigate the toxicity of TLR-DC<br /><br>and Trimix DC by dose escalation of DC numbers. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>In part II of the study, we will investigate immunological responses upon DC<br /><br>vaccination.<br /><br>Immunological responses are:<br /><br>(a) The activation of immune cells in vivo.<br /><br>(b) The immunological response induced with TLR-DC and Trimix DC loaded with<br /><br>mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase).<br /><br>Safety and clinical efficacy are secondary objectives.</p><br>