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A Dose Ranging Trial of MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured Using Cytokines With Autologous Lymphocyte Infusion With or Without Escalating Doses of Fludarabine for Patients With Chemotherapy-naive Metastatic Melanoma

Phase 1
16 Years
Not Enrolling
Intraocular Melanoma, Melanoma (Skin)

Thank you

Trial Information

A Dose Ranging Trial of MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured Using Cytokines With Autologous Lymphocyte Infusion With or Without Escalating Doses of Fludarabine for Patients With Chemotherapy-naive Metastatic Melanoma

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.

Inclusion Criteria:

- Metastatic melanoma with measurable disease after attempted curative surgical therapy
and without prior chemotherapy; adjuvant interferon or isolated limb perfusion is

- 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)

- 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

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Survival (OS)

Outcome Description:

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.

Outcome Time Frame:

3 years, 6 months

Safety Issue:


Principal Investigator

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

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

February 2006

Completion Date:

March 2012

Related Keywords:

  • Intraocular Melanoma
  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • ciliary body and choroid melanoma, medium/large size
  • recurrent intraocular melanoma
  • metastatic intraocular melanoma
  • extraocular extension melanoma
  • iris melanoma
  • Melanoma
  • Uveal Neoplasms



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612