NCT00313508

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2006

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2006

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

April 11, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 12, 2006

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed
Last Updated

February 21, 2014

Status Verified

December 1, 2012

Enrollment Period

6.1 years

First QC Date

April 11, 2006

Last Update Submit

February 20, 2014

Conditions

Keywords

stage IV melanomarecurrent melanomaciliary body and choroid melanoma, medium/large sizerecurrent intraocular melanomametastatic intraocular melanomaextraocular extension melanomairis melanoma

Outcome Measures

Primary Outcomes (1)

  • Overall Survival (OS)

    Overall Survival is defined as the time from first day of treatment to time of death due to any cause. If a patient is still alive, survival time is censored at the time of last follow-up.

    3 years, 6 months

Secondary Outcomes (2)

  • Progression-Free Survival (PFS)

    3 years, 6 months

  • Time to Progression (TTP)

    3 years, 6 months

Study Arms (2)

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

EXPERIMENTAL

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

Biological: Autologous Dendritic Cells (DC)Drug: FludarabineBiological: Autologous Lymphocyte Infusion (ALI)

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

EXPERIMENTAL

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

Biological: Autologous Dendritic Cells (DC)Drug: FludarabineBiological: Autologous Lymphocyte Infusion (ALI)

Interventions

Given intranodally

Also known as: 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.
A: Peptide-pulsed DC, ALI and Low Dose FludarabineB: Peptide-pulsed DC, ALI and High Dose Fludarabine

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

Also known as: fludarabine phosphate, FLUDARA
A: Peptide-pulsed DC, ALI and Low Dose FludarabineB: Peptide-pulsed DC, ALI and High Dose Fludarabine

Infusion

Also known as: ALI
A: Peptide-pulsed DC, ALI and Low Dose FludarabineB: Peptide-pulsed DC, ALI and High Dose Fludarabine

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612-9497, United States

Location

MeSH Terms

Conditions

Uveal MelanomaMelanoma

Interventions

Heart Rategp100 Melanoma AntigenCTAG1B protein, humanMAGEA3 protein, humanMonophenol Monooxygenasefludarabinefludarabine phosphate

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasUveal NeoplasmsEye NeoplasmsNeoplasms by SiteEye DiseasesUveal DiseasesSkin NeoplasmsSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vital SignsPhysical ExaminationDiagnostic Techniques and ProceduresDiagnosisHemodynamicsCardiovascular Physiological PhenomenaCirculatory and Respiratory Physiological PhenomenaMembrane ProteinsProteinsAmino Acids, Peptides, and ProteinsMelanoma-Specific AntigensNeoplasm ProteinsAntigens, NeoplasmAntigensBiological FactorsCatechol OxidaseMixed Function OxygenasesOxygenasesOxidoreductasesEnzymesEnzymes and Coenzymes

Study Officials

  • Jeffrey S. Weber, M.D., Ph.D.

    H. Lee Moffitt Cancer Center and Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 11, 2006

First Posted

April 12, 2006

Study Start

February 1, 2006

Primary Completion

March 1, 2012

Study Completion

March 1, 2012

Last Updated

February 21, 2014

Record last verified: 2012-12

Locations