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Dendritic Cell Vaccination During Lymphoid Reconstruction

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ClinicalTrials.gov Identifier: NCT00313508
Recruitment Status : Completed
First Posted : April 12, 2006
Last Update Posted : February 21, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.


Condition or disease Intervention/treatment Phase
Intraocular Melanoma Melanoma (Skin) Biological: Autologous Dendritic Cells (DC) Drug: Fludarabine Biological: Autologous Lymphocyte Infusion (ALI) Phase 1

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2006
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012


Arm Intervention/treatment
Experimental: A: Peptide-pulsed DC, ALI and Low Dose Fludarabine
Fludarabine: 5 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion
Biological: Autologous Dendritic Cells (DC)
Given intranodally
Other Names:
  • 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.

Drug: Fludarabine
Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.
Other Names:
  • fludarabine phosphate
  • FLUDARA

Biological: Autologous Lymphocyte Infusion (ALI)
Infusion
Other Name: ALI

Experimental: B: Peptide-pulsed DC, ALI and High Dose Fludarabine
Fludarabine: 25 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion
Biological: Autologous Dendritic Cells (DC)
Given intranodally
Other Names:
  • 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.

Drug: Fludarabine
Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.
Other Names:
  • fludarabine phosphate
  • FLUDARA

Biological: Autologous Lymphocyte Infusion (ALI)
Infusion
Other Name: ALI




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 3 years, 6 months ]
    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.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 3 years, 6 months ]
    Progression-Free Survival is defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. Evaluation of target lesions: Progressive Disease (PD)- At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  2. Time to Progression (TTP) [ Time Frame: 3 years, 6 months ]
    Time to Progression is defined as the time from first day of treatment to the first observation of disease progression or death due to disease. If failure has not occurred, failure time is censored at the time of last follow-up. Evaluation of target lesions: Progressive Disease (PD)- At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00313508


Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jeffrey S. Weber, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00313508     History of Changes
Other Study ID Numbers: MCC-13649
NCI-6241 ( Other Identifier: NCI Protocol Number )
First Posted: April 12, 2006    Key Record Dates
Last Update Posted: February 21, 2014
Last Verified: December 2012

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
stage IV melanoma
recurrent melanoma
ciliary body and choroid melanoma, medium/large size
recurrent intraocular melanoma
metastatic intraocular melanoma
extraocular extension melanoma
iris melanoma

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Fludarabine
Fludarabine phosphate
Vidarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents