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MelanomaPhase 1/2NCT00847106

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

A Phase 1/2 study testing Daclizumab and Dendritic cells in people with Melanoma, run by Radboud University Medical Center.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Melanoma
What is being tested?
Daclizumab and Dendritic cells
How many people
15 participants
Where
No sites listed yet
Study dates
Mar 2004to Oct 2005
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.
  • No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.
  • No previous treatment with monoclonal antibodies.
  • No concomitant use of corticosteroids or other immunosuppressive agents.
  • 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.
  • No serious concomitant disease, no active infections. Specifically, patients with autoimmune disease or organ allografts, and HBsAg or HIV positive patients are excluded.
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  • Patients with a known allergy to shell fish (contains KLH) are excluded.
  • Patients with asthma or severe allergic disease necessitating medication are excluded
  • No pregnant or lactating women.

About this study

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.

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.

Conditions
Melanoma
Being tested
Daclizumab, Dendritic cells
Keywords
Dendritic Cells, Regulatory T cells, CD25, Melanoma, Immunotherapy, Daclizumab, Stage IV Melanoma
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaclizumabDrug

  • Dendritic cellsBiological

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immune reponse

Secondary outcomes (1)

  1. Clinical Response

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2009 (estimated)
  2. Study startMar 2004
  3. Primary completionOct 2005
  4. Study completionOct 2005

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00847106
Sponsor's protocol ID
2003-2893
Other IDs
KWF 2003-2893
Status last verified
Feb 2009
First submitted
18 Feb 2009
Last updated
19 Feb 2009
Results posted
No

Publications

  • Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, Toes RE, Offringa R, Melief CJ. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med. 2001 Sep 17;194(6):823-32. doi: 10.1084/jem.194.6.823.

    PubMed 11560997

  • 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.

    PubMed 16110035

  • 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.

    PubMed 12517769

  • 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.

    PubMed 15477299

  • 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.

    PubMed 15122249

  • 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.

    PubMed 14613986

  • 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.

    PubMed 12218781

  • 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.

    PubMed 15766677

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Daclizumab and Dendritic cells in people with Melanoma, run by Radboud University Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune reponse. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00847106, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2009.

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