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

Melanoma Stage III or IV Clinical Trial

Official title:

In Vivo Responses of DC Vaccines Presenting HLA Class I and II Restricted Tumor Epitopes Either by Peptide-pulsing or mRNA Transfection in Melanoma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00243529
• Other study ID #: 2003-2917
• Secondary ID: KWF 2003-2917
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 21, 2005
• Last updated: September 28, 2009
• Start date: April 2004

Study information

• Verified date: February 2009
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma Stage III or IV

Intervention

Biological:
• autologous dendritic cell vaccine

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Center	Nijmegen	PO Box 9101

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

References & Publications (7)

Adema GJ, de Vries IJ, Punt CJ, Figdor CG. Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol. 2005 Apr;17(2):170-4. Review. — View Citation

de Vries IJ, Bernsen MR, Lesterhuis WJ, Scharenborg NM, Strijk SP, Gerritsen MJ, Ruiter DJ, Figdor CG, Punt CJ, Adema GJ. Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol. 2005 Aug 20;23(24):5779-87. — View Citation

de Vries IJ, Eggert AA, Scharenborg NM, Vissers JL, Lesterhuis WJ, Boerman OC, Punt CJ, Adema GJ, Figdor CG. Phenotypical and functional characterization of clinical grade dendritic cells. J Immunother. 2002 Sep-Oct;25(5):429-38. — View Citation

De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, Adema GJ, Punt CJ, Figdor CG. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res. 2003 Jan 1;63(1):12-7. — View Citation

de Vries IJ, Lesterhuis WJ, Scharenborg NM, Engelen LP, Ruiter DJ, Gerritsen MJ, Croockewit S, Britten CM, Torensma R, Adema GJ, Figdor CG, Punt CJ. Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res. 2003 Nov 1;9(14):5091-100. — View Citation

Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. Review. — View Citation

Lesterhuis WJ, de Vries IJ, Adema GJ, Punt CJ. Dendritic cell-based vaccines in cancer immunotherapy: an update on clinical and immunological results. Ann Oncol. 2004;15 Suppl 4:iv145-51. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune response		first 10 years	No
Secondary	Safety		first 10 years	Yes

External Links

•   Home page of the Radboud University Nijmegen Medical Centre
•   Website of the department of Tumor immunology of the Nijmegen Centre for Molecular Life Sciences of the Radboud University Nijmegen Medical Centre