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Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00683670
First received: May 19, 2008
Last updated: February 21, 2017
Last verified: February 2017
  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
Intervention Model: Parallel Assignment
Masking: No masking
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 University of Pennsylvania:

Primary Outcome Measures:
  • 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 ]
    • 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.
    • Data are presented as the percentage of CD8+ T cells positive for tetramer binding based on gating variables set using the iMASC reagent kit (Beckman Coulter).

  • Safety and tolerability of the mature dendritic cell vaccine as measured by adverse events [ Time Frame: 30 days after end of treatment ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: Through completion of treatment or until progressive disease ]
  • Regulatory T cell depletion after cyclophosphamide administration. [ Time Frame: Day -3 (72 hours prior to vaccine dose 1) ]
    Regulatory T cells (Treg) are defined as CD4+CD25+foxP3+ (triple positive) cells. At the indicated time points, the percentage of Treg cells is determined by 3 color flow cytometry. The depletion of Treg is defined as follows [Treg baseline - Treg nadir/ Treg baseline x 100= % depletion].

  • 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) ]
  • Clinical response rate using RECIST criteria [ Time Frame: After third vaccine, sixth vaccine, and then every 8 weeks ]

Enrollment: 17
Study Start Date: August 2008
Study Completion Date: June 2016
Primary Completion Date: June 2016 (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
Experimental: Dendritic Cell Vaccine (Third 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 6 weeks for a total of 3 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 in order to collect PBMC for immune monitoring.
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   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • 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 +/- MEK 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, anti-PD1, 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00683670

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Gerald P. Linette, M.D., Ph.D. Abramson Cancer Center of the University of Pennsylvania
  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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00683670     History of Changes
Other Study ID Numbers: 07-0652 / 826850
Study First Received: May 19, 2008
Last Updated: February 21, 2017

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
Vaccines
Cyclophosphamide
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 24, 2017