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Dendritic Cell Vaccination During Lymphoid Reconstruction

Primary Purpose

Intraocular Melanoma, Melanoma (Skin)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous Dendritic Cells (DC)
Fludarabine
Autologous Lymphocyte Infusion (ALI)
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intraocular Melanoma focused on measuring stage IV melanoma, recurrent melanoma, ciliary body and choroid melanoma, medium/large size, recurrent intraocular melanoma, metastatic intraocular melanoma, extraocular extension melanoma, iris melanoma

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

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

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression-Free Survival (PFS)
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.
Time to Progression (TTP)
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.

Full Information

First Posted
April 11, 2006
Last Updated
February 20, 2014
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00313508
Brief Title
Dendritic Cell Vaccination During Lymphoid Reconstruction
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 Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
February 2006 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intraocular Melanoma, Melanoma (Skin)
Keywords
stage IV melanoma, recurrent melanoma, ciliary body and choroid melanoma, medium/large size, recurrent intraocular melanoma, metastatic intraocular melanoma, extraocular extension melanoma, iris melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: Peptide-pulsed DC, ALI and Low Dose Fludarabine
Arm Type
Experimental
Arm Description
Fludarabine: 5 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion
Arm Title
B: Peptide-pulsed DC, ALI and High Dose Fludarabine
Arm Type
Experimental
Arm Description
Fludarabine: 25 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion
Intervention Type
Biological
Intervention Name(s)
Autologous Dendritic Cells (DC)
Other Intervention Name(s)
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.
Intervention Description
Given intranodally
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
fludarabine phosphate, FLUDARA
Intervention Description
Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.
Intervention Type
Biological
Intervention Name(s)
Autologous Lymphocyte Infusion (ALI)
Other Intervention Name(s)
ALI
Intervention Description
Infusion
Primary Outcome Measure Information:
Title
Overall Survival (OS)
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.
Time Frame
3 years, 6 months
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
3 years, 6 months
Title
Time to Progression (TTP)
Description
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.
Time Frame
3 years, 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey S. Weber, M.D., Ph.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States

12. IPD Sharing Statement

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Dendritic Cell Vaccination During Lymphoid Reconstruction

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