Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 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: February 25, 2015
Last verified: February 2015

May 19, 2008
February 25, 2015
August 2008
February 2016   (final data collection date for primary outcome measure)
  • 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.
    • 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 ] [ Designated as safety issue: Yes ]
    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.
To determine the immunological response based on measuring increased numbers of peptide specific CD8+ T cells as calculated by the tetramer assay. [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00683670 on ClinicalTrials.gov Archive Site
  • Time to progression [ Time Frame: Through completion of treatment or until progressive disease ] [ Designated as safety issue: No ]
  • Regulatory T cell depletion after cyclophosphamide administration. [ Time Frame: Day -3 (72 hours prior to vaccine dose 1) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
  • Clinical response rate using RECIST criteria [ Time Frame: After third vaccine, sixth vaccine, and then every 8 weeks ] [ Designated as safety issue: No ]
  • To determine the time to progression [ Designated as safety issue: No ]
  • To assess regulatory T cell depletion after cyclophosphamide administration. [ Designated as safety issue: No ]
  • To perform exploratory biomarker analysis of accessible tumors [ 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. [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Dendritic Cells (White Blood Cells) Vaccination for Advanced Melanoma
Mature Dendritic Cell Vaccination Against gp100 in Patients With Advanced Melanoma

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • Drug: cyclophosphamide
    Other Name: Cytoxan
  • Biological: Mature dendritic cell vaccine
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • 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.
    Interventions:
    • Drug: cyclophosphamide
    • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Biological: Mature dendritic cell vaccine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
August 2016
February 2016   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Gerald P Linette, M.D., Ph.D. 314-362-5677 glinette@dom.wustl.edu
United States
 
NCT00683670
07-0652 / 201103308
Yes
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Gerald P. Linette, M.D., Ph.D. Washington University School of Medicine
Washington University School of Medicine
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP