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 May 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: May 31, 2013

Last verified: May 2013

History of Changes

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:

MedlinePlus related topics: Melanoma

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

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:	September 2013
Estimated Primary Completion Date:	August 2013 (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

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)

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 School of Medicine

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

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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:	May 31, 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 June 17, 2013

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