Augmentation of Dendritic Cell-Based Vaccines in Melanoma Patients by Depletion of Regulatory T Cells in Stage IV Melanoma Patients

This study has been completed.
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00847106
First received: February 18, 2009
Last updated: NA
Last verified: February 2009
History: No changes posted
  Purpose

Dendritic cells (DC) are the professional antigen presenting cells of the immune system. Multiple distinct DC lineage's exist and it is now well appreciated that the DC subset and the maturation stage of the DC determines the type of immune response, ranging from a TH1 or TH2 response to immune tolerance. The extremely potent capacity of mature DC to initiate immune responses can be exploited to fight infectious diseases and cancer. Others and we are currently using tumor antigen loaded mature DC in clinical vaccination studies against cancer, and clinical as well as immunological responses have been observed.

Exciting new insights accompany the revival of suppressor T cells, now referred to as regulatory T cells (Treg), and implicate that also Treg play a key role in the control of immunity. Treg constitute a sub-population of CD4+ T cells constitutively expressing the IL-2R alpha-chain (CD25). Treg show remarkably suppressive activities on different components of the immune system, including T lymphocytes and dendritic cells, suggesting they act both at the initiation phase (DC) and at the effector phase (activated T cells) of the immune response. Interestingly, temporal depletion of Treg has been shown to enhance anti-tumor immune responses and in case of prolonged absence of Treg even autoimmunity. Furthermore, data in mouse tumor models indicate that temporal depletion of Treg also results in improved vaccine efficiency in the therapeutic setting, e.g. in mice with a pre-existing tumor. These data imply that in tumor bearing patients depletion of Treg prior to vaccination will improve vaccine efficacy.

In this study we investigate the effect of regulatory T cell (Treg) depletion on the efficacy of DC-based anti-tumor vaccines in a clinical study using melanoma associated antigens tyrosinase and gp100-loaded DC and a depleting anti-CD25 mononuclear antibody (Daclizumab). Our primary objective in this study is the induction of an effective anti-tumor immune response. Our secondary objective is the induction of a clinical response.


Condition Intervention Phase
Melanoma
Drug: Daclizumab
Biological: Dendritic cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Augmentation of Dendritic Cell Based Vaccines in Melanoma Patients by Depletion of Regulatory T Cells With an Anti-CD25 Monoclonal Antibody (Daclizumab). A Clinical Study.

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Immune reponse

Secondary Outcome Measures:
  • Clinical Response

Estimated Enrollment: 15
Study Start Date: March 2004
Estimated Study Completion Date: October 2005
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically documented evidence of melanoma.
  2. Stage IV melanoma according to the 2001 AJCC criteria. [53] Limited tumor burden; LDH < 2x upper limit of normal.
  3. HLA-A2.1 phenotype according to lymphocyte HLA typing.
  4. Expression of gp100 and/or tyrosinase on melanoma cells, as detected by immunohistochemistry, preferably on metastatic tumor, but if not available on primary tumor.
  5. ECOG performance status 0-1, life expectancy > 3 months.
  6. Age 18-75 years. -
  7. Written informed consent.
  8. Expected adequacy of follow-up.
  9. 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.

    Exclusion Criteria:

  10. No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases CT scan of the brain should be performed to exclude this.
  11. No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.
  12. No previous treatment with monoclonal antibodies.
  13. No concomitant use of corticosteroids or other immunosuppressive agents.
  14. No history of second malignancy within the last 5 years. Adequately treated basal carcinoma of skin or carcinoma in situ of cervix is acceptable within this period.
  15. No serious concomitant disease, no active infections. Specifically, patients with autoimmune disease or organ allografts, and HBsAg or HIV positive patients are excluded.
  16. Patients with a known allergy to shell fish (contains KLH) are excluded.
  17. Patients with asthma or severe allergic disease necessitating medication are excluded
  18. No pregnant or lactating women.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00847106

Sponsors and Collaborators
Radboud University
Dutch Cancer Society
Investigators
Principal Investigator: Prof. C.J.A. Punt, MD, PhD Radboud University
Principal Investigator: Prof. G.J. Adema, PhD Radboud University
  More Information

Additional Information:
Publications:

ClinicalTrials.gov Identifier: NCT00847106     History of Changes
Other Study ID Numbers: 2003-2893, KWF 2003-2893
Study First Received: February 18, 2009
Last Updated: February 18, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Dendritic Cells
Regulatory T cells
CD25
Melanoma
Immunotherapy
Daclizumab
Stage IV Melanoma

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Daclizumab
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014