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

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00798629
• Other study ID #: MCC-15280
• Secondary ID: NCI P-8190
• Status: Completed
• Phase: Phase 1
• First received: November 25, 2008
• Last updated: September 21, 2012
• Start date: November 2008
• Est. completion date: April 2012

Study information

• Verified date: September 2012
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• Autologous dendritic cell-adenovirus CCL21 vaccine
Intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Number of Participants with Adverse Events	Toxicity as assessed by NCI CTCAE v3.0	2 years, 5 months	Yes