Immunization of patients with malignant melanoma with autologous CD34+ cell-derived dendritic cells transduced ex vivo with a recombinant replication-deficient vaccinia vector encoding the human tyrosinase gene:: A phase I trial

Protocol title: Immunization of Patients with Malignant Melanoma with Autologous CD34(+) Cell-Derived Dendritic Cells Transduced Ex Vivo with a Recombinant Nonreplicating Vaccinia Vector Encoding the Human Tyrosinase Gene: A Phase I Trial Study Phase: Phase I Study Design: Nonrandomized, noncontrolled, single center Study Objectives: Primary objective: Define the safety and toxicity of DCs/MVA-hTyr vaccine in patients with measurable metastatic melanoma. Secondary objectives: ( 1) to determine whether immunization with DCs/MVA-hTyr vaccine induces tyrosinase and melanoma-specific immune responses such as ( a) development or enhancement of T lymphocyte-mediated responses in peripheral blood; (b) measurable delayed-type hypersensitivity (DTH) response in vivo; ( c) development of anti-tyrosinase antibodies in serum of treated patients; and (d) infiltration and expansion of tyrosinase-specific T lymphocytes in the inoculation site; and ( 2) to document any tumor regression and/or pigmentation modification that may result from immunization against tyrosinase Number of Subjects: The total number of patients expected to complete this study is six Study Population: Patients with malignant melanoma stage IV or high-risk stage III with measurable metastatic melanoma Treatment Groups: Four vaccinations containing 100 x 10(6) DCs/MVA-hTyr will be given four times at 2-week intervals; the 1degrees vaccination will be given intravenously; the 2degrees, 3degrees, and 4degrees vaccinations will be given subcutaneously Duration of Study: 20 weeks Visit Schedule: Screening visit(s) Admission to the general clinical research center and baseline studies Preparative phase with the administration of filgrastim for six consecutive days followed by leukapheresis Immunization phase Follow-up visits monthly for 3 months and then at 2-month intervals for survival and general condition until death Safety parameters: Physical examination and measurements of melanoma lesions Complete blood tests Antimelanoma T lymphocyte ( both CD8(+) and CD4(+)) responses Ophthalmology evaluation including fundoscopy and visual acuity Neurological evaluation Cardiac rhythm, including Holter Efficacy Parameters: Tumor response and time to progression by physical examination and CT scan Progression-free survival Overall survival Hypopigmentation Immunological evaluation: Melanoma antigen-specific and/or melanoma-specific CTL precursor frequency; antigen-specific HLA class II-restricted T cell responses; anti-tyrosinase antibodies in serum of treated patients; whenever possible biopsy at the site of vaccination to evaluate the infiltrate.