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

NCT00243529 | Completed Phase 1

• 2 other identifiers: 2003-2917KWF 2003-2917
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma Stage III or IV

Keywords

Dendritic cells; Melanoma; Vaccine; Immunotherapy; RNA; Peptides

Outcome Measures

Primary Outcomes (1)

• Immune response

  first 10 years

Secondary Outcomes (1)

• Safety

  first 10 years

Study Arms (3)

MHC Class I restricted epitopes

ACTIVE COMPARATOR

HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase

Biological: autologous dendritic cell vaccine

MHC Class I and II restricted epitopes

EXPERIMENTAL

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

Biological: autologous dendritic cell vaccine

mRNA transfected DC

EXPERIMENTAL

HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase

Biological: autologous dendritic cell vaccine

Interventions

autologous dendritic cell vaccine BIOLOGICAL

MHC Class I and II restricted epitopes; MHC Class I restricted epitopes; mRNA transfected DC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Center

Nijmegen, PO Box 9101, 6500 HB, Netherlands

Location

Related Publications (7)

• 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. doi: 10.1200/JCO.2005.06.478.

  PMID: 16110035 BACKGROUND

• 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. doi: 10.1093/annonc/mdh919. No abstract available.

  PMID: 15477299 BACKGROUND

• Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. doi: 10.1038/nm1039.

  PMID: 15122249 BACKGROUND

• 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.

  PMID: 14613986 BACKGROUND

• 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.

  PMID: 12517769 BACKGROUND

• 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. doi: 10.1097/00002371-200209000-00007.

  PMID: 12218781 BACKGROUND

• 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. doi: 10.1016/j.coi.2005.01.004.

  PMID: 15766677 BACKGROUND

Related Links

• Home page of the Radboud University Nijmegen Medical Centre

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Prof. C.J.A. Punt, MD, PhD

  Radboud University Nijmegen Medical Center

  PRINCIPAL INVESTIGATOR

• Prof. G.J. Adema, PhD

  Radboud University Nijmegen Medical Center/Nijmegen Center for Molecular Life Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 21, 2005
• First Posted: October 24, 2005
• Study Start: April 1, 2004
• Primary Completion: February 1, 2009
• Last Updated: September 29, 2009

Record last verified: 2009-02

Locations

NL (1)