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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00847106
Recruitment Status : Completed
First Posted : February 19, 2009
Last Update Posted : February 19, 2009
Dutch Cancer Society
Information provided by:
Radboud University Medical Center

Brief Summary:

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 or disease Intervention/treatment Phase
Melanoma Drug: Daclizumab Biological: Dendritic cells Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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.
Study Start Date : March 2004
Actual Primary Completion Date : October 2005
Study Completion Date : October 2005

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma Vaccines
Drug Information available for: Daclizumab

Primary Outcome Measures :
  1. Immune reponse

Secondary Outcome Measures :
  1. Clinical Response

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00847106

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

Layout table for additonal information Identifier: NCT00847106    
Other Study ID Numbers: 2003-2893
KWF 2003-2893
First Posted: February 19, 2009    Key Record Dates
Last Update Posted: February 19, 2009
Last Verified: February 2009
Keywords provided by Radboud University Medical Center:
Dendritic Cells
Regulatory T cells
Stage IV Melanoma
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs