Evaluating the Safety and the Biological Effects of Intratumoral Interferon Gamma and a Peptide-Based Vaccine in Patients With Melanoma (Mel 51)
|Melanoma||Biological: A combination of intratumoral IFN-gamma plus systemic vaccination with MELITAC 12.1||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Evaluation of the Safety and Immunogenicity of Intratumoral Injection of Interferon Gamma During Vaccination in Patients With Subcutaneous or Cutaneous Metastases of Melanoma|
- Safety: To determine the safety of administration of intratumoral interferon gamma with a peptide-based vaccine in patients with cutaneous or subcutaneous metastases of melanoma. [ Time Frame: 6 months ]
- Biologic effect: To evaluate the biological effects of vaccine plus IFN-gamma at the tumor site, to include expression of CXCR3 ligands (CXCL9, CXCL10 & CXCL11) and the magnitude of infiltration of CD8+ CXCR3+ T cells and vaccine-specific T cells. [ Time Frame: 6 months ]
- To estimate the effects of vaccine on CXCR3 expression by circulating antigen-experienced CD4 and CD8 T cells. [ Time Frame: 6 months ]
- To estimate the effects of vaccine plus IFN-gamma on changes in the percentage of FoxP3+ CD25hi CD4+ (putative regulatory T cells, T regulatory cells) among tumor infiltrating T cells. [ Time Frame: 6 months ]
- To obtain preliminary data on the variability of immunologic parameters among multiple biopsies of subcutaneous or cutaneous metastases of melanoma. [ Time Frame: 6 months ]
- To obtain preliminary data on the clinical response of cutaneous or subcutaneous metastases of melanoma to the proposed combination regimen. [ Time Frame: 6 months ]
|Study Start Date:||November 2009|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: intratumoral IFN-gamma plus MELITAC 12.1,
intratumoral IFN-gamma plus systemic vaccination with MELITAC 12.1, an emulsion of a mixture of 12 class I MHC-restricted melanoma-derived peptides (12-MP) and a class II MHC-restricted tetanus toxoid-derived helper peptide (Peptide-tet).
Biological: A combination of intratumoral IFN-gamma plus systemic vaccination with MELITAC 12.1
Vaccine regimen: The vaccines will be administered in two treatment cycles. During cycle one, three vaccines will be administered over a 3-week period on days 1, 8, 15. During cycle two, three vaccines will be administered over a 9-week period on days 24, 43, 64. All participants will receive 12-MP (100 mcg each peptide) plus Peptide-tet (Peptide-tet; 200 mcg) administered in Montanide ISA-51 VG adjuvant. The vaccine will be administered subcutaneously (1 ml) and intradermally (1ml) at a single vaccination site.
Intratumoral Interferon regimen: On day 22, patients will have one or more tumor sites injected with 0.5-2 million IU of IFN-gamma each, with a maximum dose of 2 million IU of IFN-gamma administered per patient. The number of lesions that are injected will be dependent on the availability and size of the lesions.
Melanoma vaccines have been associated with major regressions in a small percentage of patients with advanced measurable disease. This provides proof-of-principle of the potential for clinical benefit with melanoma vaccines however, the current response rate is low. Thus, there is a critical need for additional new therapies for melanoma, both for adjuvant therapy of high-risk resected melanoma and for therapy of patients who are not candidates for, or fail, other therapies in the setting of advanced disease.
It is generally agreed that one mechanism to improve the immunologic outcomes of vaccine therapy is to optimize T cell trafficking to the tumor site. CXCR3 is the chemokine receptor on T cells which directs them to sites of inflammation by following the chemokine gradient. The ligands for CXCR3 (CXCL9 (MIG), CXCL10 (IP-10) and CXCL11 (I-TAC)) are known to be induced by interferon gamma. This protocol proposes administering a peptide vaccine to activate tumor antigen-specific CD8+ T cells expressing CXCR3, followed by intratumoral interferon gamma to increase CXCR3 ligands (CXCL9-11) at the tumor site and recruit the CXCR3+ T cells.
The primary goals of the proposed work are to assess the safety of the combination of peptide vaccine and intratumoral interferon gamma and to assess the immunologic outcomes at the tumor site.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00977145
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Craig L. Slingluff, M.D.||University of Virginia|