Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

Phase 1

Completed

• Conditions: Melanoma Stage III or IV
• Interventions: Biological: autologous dendritic cell vaccine

• Registration Number: NCT00243529
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-04
• Study First Submitted: 2005-10-21
• Study First Submitted QC: 2005-10-21
• Study First Posted: 2005-10-24
• Status Verified: 2009-02
• Primary Completion: 2009-02
• Last Update Submitted: 2009-09-28
• Last Update Posted: 2009-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

For both stage III and IV

• Histological proof of cutaneous melanoma
• Melanoma expressing both gp100 and tyrosinase, each in approximately 20% or more of cells by immunohistochemistry staining,
• HLA type A2 and/or A3, with known HLA-DR4 expression,
• WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l.
• Expected adequacy of follow-up,
• Written informed consent.

For Stage III only

• Stage III melanoma according to the 2001 AJCC criteria.
• Start of treatment within 2 months of lymph node dissection for melanoma stage III

For stage IV only

-Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal

Exclusion Criteria

For both stage III and IV

• No autoimmune disorders, no concomitant use of immunosuppressive drugs,
• no serious concomitant disease, no serious active infections, no other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin,
• No known allergy to shell fish (contains KLH) are excluded.
• No pregnancy or lactation,

For stage III only:

• No signs or symptoms of distant metastases as defined by normal history, physical examination, chest X-ray and serum LDH.
• No concomitant or previous systemic treatment for melanoma

For stage IV only:

• No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this.
• No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MHC Class I restricted epitopes	autologous dendritic cell vaccine	HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase
MHC Class I and II restricted epitopes	autologous dendritic cell vaccine	HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase
mRNA transfected DC	autologous dendritic cell vaccine	HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase

Primary Outcome Measures

Name	Time	Method
Immune response	first 10 years

Secondary Outcome Measures

Name	Time	Method
Safety	first 10 years

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Center; 🇳🇱 Nijmegen, PO Box 9101, Netherlands