Dendritic Cell Vaccination During Lymphoid Reconstruction

NCT ID: NCT00313508

Last Updated: 2014-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-02-28

Study Completion Date

2012-03-31

Brief Summary

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This is a randomized, controlled, multicenter, dose-escalation study of fludarabine. Patients are randomized to 1 of 2 treatment arms.

The purpose of this study is to find out what side effects are caused in this study and whether Fludarabine with the dendritic cell vaccine (DC vaccine) can increase the ability of the immune system to recognize melanoma.

Detailed Description

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This is a dose ranging study of intranodal administration of autologous dendritic cells (DC) pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100 (209-217 (210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215 as well as class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase (450-462) peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses of Fludarabine. The nine or ten amino acid peptides representing HLA-A2 restricted T cell epitopes of MART-1, gp100, NY-ESO-1 and tyrosinase will be pulsed onto autologous dendritic cells produced by incubation of peripheral blood mononuclear cells obtained by apheresis with interleukin-4 (IL-4) and GM-CSF and pulsed with four helper peptides then matured with a cytokine cocktail including TNF-a, IL-6, IL-1b and PGE2. Melanoma antigen peptide-pulsed dendritic cells will be administered at a total dose of 10 million cells each for four intranodal injections to patients with chemotherapy-naïve metastatic melanoma.

DC matured with a cytokine cocktail and pulsed with class I and II peptides will be injected intranodally, weekly for two doses, then every two weeks for two doses, for a total of four injections to each cohort.

Conditions

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Intraocular Melanoma Melanoma (Skin)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A: Peptide-pulsed DC, ALI and Low Dose Fludarabine

Fludarabine: 5 mg/m\^2/day, Auto Lymphocyte Infusion, DC Infusion

Group Type EXPERIMENTAL

Autologous Dendritic Cells (DC)

Intervention Type BIOLOGICAL

Given intranodally

Fludarabine

Intervention Type DRUG

Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.

Autologous Lymphocyte Infusion (ALI)

Intervention Type BIOLOGICAL

Infusion

B: Peptide-pulsed DC, ALI and High Dose Fludarabine

Fludarabine: 25 mg/m\^2/day, Auto Lymphocyte Infusion, DC Infusion

Group Type EXPERIMENTAL

Autologous Dendritic Cells (DC)

Intervention Type BIOLOGICAL

Given intranodally

Fludarabine

Intervention Type DRUG

Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.

Autologous Lymphocyte Infusion (ALI)

Intervention Type BIOLOGICAL

Infusion

Interventions

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Autologous Dendritic Cells (DC)

Given intranodally

Intervention Type BIOLOGICAL

Fludarabine

Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.

Intervention Type DRUG

Autologous Lymphocyte Infusion (ALI)

Infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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Autologous Dendritic Cells (DC) pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100 (209-217 (210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215 as well as class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase (450-462) peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses of Fludarabine. fludarabine phosphate FLUDARA ALI

Eligibility Criteria

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Inclusion Criteria

* Metastatic melanoma with measurable disease after attempted curative surgical therapy and without prior chemotherapy; adjuvant interferon or isolated limb perfusion is allowed.
* Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-1/tyrosinase/NY-ESO-1 by immunohistochemical staining and will also be stained for HMB-45 by immunohistochemistry, and positivity for at least one will be an entry requirement.
* Patients must be HLA-A \*0201 positive by a DNA polymerase chain reaction (PCR) analysis.
* Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and alanine transaminase/aspartic transaminase (ALT/AST) of less than 3X institutional upper limit of normal (ULN).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Patients must be able to understand and sign an Institutional Review Board (IRB) approved informed consent form.
* Patients must have whit blood count (WBC) of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more.
* Patients must be seropositive for Epstein-Barr virus (EBV).
* Patients with unresectable stages III/IV uveal melanoma and metastatic mucosal melanoma will be eligible for this trial.

Exclusion Criteria

* Patients who are undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy.
* Have major systemic infections, coagulation disorders, or other major medical illnesses (MI) of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months.
* Require steroid therapy.
* Are pregnant or lactating.
* Are known to be positive for hepatitis BsAg, Hepatitis C or human immunodeficiency virus (HIV) antibody, since cells for DC cannot be grown in the laboratory when virus contaminated.
* Have a prior history of uveitis or autoimmune inflammatory eye disease.
* Have previously received the gp100 209-217 (210M), MART-1 26-35 (27L), gp100 280-288 (288V), tyrosinase 207-215 or NY-ESO-1 157-165 (165V) peptides.
* Have had another malignancy other than cervical carcinoma-in-situ or basal cell

/squamous cancer of the skin, unless they have undergone curative therapy more than 5 years ago and are still free of detectable disease.
* Since this trial increase the risk of immunological impairment, patients with the following will be excluded from this trial: Hypogammaglobulinemia, Lymphocytopenia, History of impaired immune response, tuberculosis (TB) or positive purified protein derivative (PPD) unless they have received BCG vaccine.
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeffrey S. Weber, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

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H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-6241

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-13649

Identifier Type: -

Identifier Source: org_study_id

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