Adenovirus CCL-21 Transduced MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured

A Dose Ranging Trial of Adenovirus CCL-21 Transduced MART-1/gp100 Peptide-Pulsed Dendritic Cells Matured Using Cytokines for Patients With Chemotherapy-Resistant Metastatic Melanoma

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: Autologous dendritic cell-adenovirus CCL21 vaccine

Detailed Description

In this phase I study, patients will receive intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC with total volumes for each intradermal injection of no more than 1 ml to be split into four injections of 0.25 ml each in four limbs in node draining areas (proximal arms and thighs), for a total DC dose of 2 X 10^6, 10^7 or 2 X 10^7 cells to be administered intradermally. DC injections in one course of therapy will be given four times at intervals of weekly for two doses (days 1 and 8 +/- 72 hrs.), then every two weeks for two doses (at days 22 +/- 72 hrs. and 36 +/- 72 hours). Cells will be harvested for DC administration and a flow cytometry analysis as well as microbiologic analysis including bacterial/fungal cultures and gram stain will be performed prior to infusion. All injections will be based on number of DC, not number of total cells.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Metastatic melanoma with measurable disease after attempted curative surgical therapy and who have received at least one prior chemotherapy regimen; adjuvant interferon or isolated limb perfusion is allowed.
• Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-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 SSOP analysis.
• Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and ALT/AST of less than 3X institutional upper limit of normal.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must be able to understand and sign an IRB approved informed consent form.
• Patients must have white blood count of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more.
• Patients with unresectable stages III/IV uveal melanoma and metastatic mucosal melanoma will be eligible for this trial.

Exclusion Criteria:

• 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 of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months
• Require steroid therapy
• Patients who are pregnant or lactating
• Known to be positive for hepatitis BsAg, Hepatitis C or HIV antibody
• Have a prior history of uveitis or autoimmune inflammatory eye disease
• 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 3 years ago and are still free of detectable disease, since the effects of peptide-pulsed DC on other active cancers are unknown

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine Dose Escalation; Dose Escalation: Intradermal DC Injection. Level 1: Cell Dose: 2 x 10^6 Level 2: Cell Dose: 1 x 10^7 Level 3: Cell Dose: 2 x 10^7	Biological: Autologous dendritic cell-adenovirus CCL21 vaccine; Intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC; Other Names: NSC 709401; NSC 683472; gp100:209-217(210M)Peptide; MART-1:26-35(27L)Peptide; dendritic cell (DC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Immune response	Assessment of immune responses to the cytokine-cocktail-matured class I peptide-pulsed adenoviral CCL-21 transduced DC cell vaccine. Immune reactivity will be monitored for the appearance of lymphoid-like structures at the vaccine site (as a result of CCL-21 production), in the blood for MART-1 /gp100 specific T cell frequency by tetramer based flow cytometry and ELISPOT analysis of fresh cells, and CTL cytolytic reactivity after in vitro sensitization prior to, four weeks after, and 8 weeks after immunization.	2 years, 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Toxicity as assessed by NCI CTCAE v3.0	2 years, 5 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jeffrey S. Weber, MD, PhD, H. Lee Moffitt Cancer Center and Research Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: November 25, 2008
• First Submitted That Met QC Criteria: November 25, 2008
• First Posted (Estimate): November 26, 2008

Study Record Updates

• Last Update Posted (Estimate): September 24, 2012
• Last Update Submitted That Met QC Criteria: September 21, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; mucosal melanoma; stage III melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: MCC-15280; NCI P-8190 (Other Grant/Funding Number: NCI)