Trial record 1 of 1 for:    NCT00683670
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Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma

This study is currently recruiting participants.
Verified December 2013 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00683670
First received: May 19, 2008
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to investigate a method of using dendritic cells (a kind of white blood cell) as a vaccine to stimulate your own immune system to react to your melanoma cells.


Condition Intervention Phase
Melanoma
Drug: cyclophosphamide
Biological: Mature dendritic cell vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mature Dendritic Cell Vaccination Against gp100 in Patients With Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • To determine the immunological response based on measuring increased numbers of peptide specific CD8+ T cells as calculated by the tetramer assay. [ Time Frame: Through completion of treatment ] [ Designated as safety issue: No ]
    Starting on Day 0, two tubes will be drawn weekly until Day 64. Thereafter, two tubes will be drawn every 21 days until Day 190. For patients receiving maintenance treatment, blood is drawn every month.

  • Assess the safety and tolerability of the mature dendritic cell vaccine [ Time Frame: 30 days after end of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the time to progression [ Time Frame: Through completion of treatment or until progressive disease ] [ Designated as safety issue: No ]
  • To assess regulatory T cell depletion after cyclophosphamide administration. [ Time Frame: Day -3 (72 hours prior to vaccine dose 1) ] [ Designated as safety issue: No ]
  • To perform exploratory biomarker analysis of accessible tumors [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • To determine the safety and side effect profile of mDC administered to patients given after a single dose of cyclophosphamide. [ Time Frame: Day 0 (prior to vaccine dose 1) ] [ Designated as safety issue: Yes ]
  • Determine the clinical response rate using RECIST criteria [ Time Frame: After third vaccine, sixth vaccine, and then every 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: August 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dendritic Cell Vaccine (First Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
Drug: cyclophosphamide
Other Name: Cytoxan
Biological: Mature dendritic cell vaccine
Experimental: Dendritic Cell Vaccine (Second Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
Drug: cyclophosphamide
Other Name: Cytoxan
Biological: Mature dendritic cell vaccine

Detailed Description:

Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production. All patients will be given cyclophosphamide 300mg/m2 IV three days prior to vaccine dose #1 in order to deplete regulatory T cells. All patients will receive mature DC for each dose of vaccine. For each dose all patients will receive autologous dendritic cells pulsed with 2 gp100 melanoma peptides (G209-2M and G280-9V) plus up to an additional 10 unique melanoma tumor-specific peptides. All patients will receive booster doses with mature DC. The DC vaccine will be given intravenously every three weeks for a total of six vaccine doses. Peripheral blood (16 ml) will be taken weekly to monitor the immune response to each peptide by tetramer assay. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Restaging is performed after three and six vaccine doses. Patients with stable disease or better (partial response/complete response) after six doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unresectable stage III and stage IV M1a/M1b/M1c melanoma including patients with uveal melanoma
  • Age ≥ 18 years
  • Life expectancy ≥ 4 months
  • ECOG performance status 0-2
  • HLA-A2 positive
  • gp100 expression > 6% in primary lesion or metastasis
  • At least 28 days from prior treatment (including adjuvant interferon) except in cases of a BRAF inhibitor (such as vemurafenib); concurrent treatment with a BRAF inhibitor is permitted
  • Required initial laboratory values (submitted within 14 days prior to registration):

    • WBC >3,000/mm3
    • Hg ≥ 9.0 gm/dl Platelets >75,000/mm3 Serum Bilirubin < 2.0 mg/dl Serum Creatinine < 2.0 mg/dl
  • Sexually active women of childbearing potential must use effective birth control during the trial and for at least two months following the trial, and sexually active men must be willing to avoid fathering a new child while receiving therapy.

Exclusion Criteria:

  • Prior treatment with more than one line of cytotoxic chemotherapy; prior treatment with one line of cytotoxic chemotherapy is permitted. Prior treatment with targeted therapy (such as ipilumumab, and BRAF inhibitor) is permitted
  • Active untreated CNS metastasis
  • Active infection
  • Prior malignancy (except non-melanoma skin cancer) within 3 years
  • Pregnant or nursing
  • Concurrent treatment with corticosteroids; local (inhaled or topical) steroids are permitted.
  • Inability to provide adequate informed consent
  • Known allergy to eggs
  • Prior history or uveitis or autoimmune inflammatory eye disease.
  • Known positivity for hepatitis BsAg, hepatitis C antibody, or HIV antibody.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00683670

Contacts
Contact: Gerald P Linette, M.D., Ph.D. 314-362-5677 glinette@dom.wustl.edu

Locations
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Gerald Linette, M.D., Ph.D.    314-362-5677    glinette@dom.wustl.edu   
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: Beatriz M. Carreno, Ph.D.         
Sub-Investigator: Lynn A. Cornelius, MD         
Sub-Investigator: George Despotis, M.D.         
Sub-Investigator: Kathryn Trinkaus, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Gerald P. Linette, M.D., Ph.D. Washington University
  More Information

Additional Information:
Publications:
Jemal, A., T. Murray, E. Ward, A. Samuels, R.C. Tiwari, A. Ghafoor, E.J. Feuer, and M.J. Thun. 2007. Cancer statistics, 2007. CA Cancer J Clin 57:42-59.
Lotze, M.T., R.M. Dallal, J.M. Kirkwood, and J.C. Flickinger. 2001. Cutaneous Melanoma. In Cancer:Principles and Practice of Oncology. V.T. DeVita, S. Hellman, and S.A. Rosenberg, editors. Lippincott, Williams, & Wilkins, Philadelphia. 2012-2069.
Ernsdorf MS, C.T., and L Titus-Ernsdorf. 2003. Update: Medical therapy for cutaneous melanoma. ASCO Educational Book 39:198-207.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00683670     History of Changes
Other Study ID Numbers: 07-0652 / 201103308
Study First Received: May 19, 2008
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 17, 2014