Active Immunotherapy Of Metastatic Renal Cell Carcinoma Using Autologous Dendritic Cells Transfected With Autologous Total Tumor RNA
The feasibility and dose-limiting toxicity of administering escalating doses of dendritic cells transfected with autologous renal cell carcinoma RNA DC(DCRCC-RNA) will be defined. As a secondary endpoint, the ability of DCRCC-RNA to induce tumor-specific immune responses will be evaluated. Finally, the anti-tumor effects measured by clinical response criteria, their duration and overall survival (calculated at 2-year follow-up) will be determined in each patient receiving dendritic cell therapy.
Background: Prognosis in metastatic renal cell carcinoma is poor with a median survival of less than one year. Although renal cell carcinoma has shown some response to immunotherapy, the results of systemic administration of biologic response modifiers in disseminated renal cell carcinoma have been poor. Growing evidence suggests that active immunotherapy, particularly dendritic cells (DC) based vaccines, may prove to be a viable and clinically effective therapeutic option for patients with advanced or metastatic renal cell carcinoma.
|Study Design:||Primary Purpose: Treatment|
Methods: This study will enroll patients with renal cell carcinoma Stage III (T3 N1 M0) or Stage IV (T4 N0 N1 M0 - any T N2 M0 - any T any N M1) after nephrectomy. Peripheral blood mononuclear cells collected through leukapheresis are processed for DC generation. Mononuclear cells are separated and cultured for 7 days in GM-CSF and IL-4. Harvested DC will be pulsed with renal tumor RNA harvested during nephrectomy. An aliquot of these cells will be tested for appropriate phenotype fungal and bacterial sterility as well as for endotoxin content prior to lot release. Renal tumor RNA transfected DC will be stored cryopreserved until administration.
The first 3 patients will be enrolled at a low dose and monitored for dose limiting toxicities. If no dose limiting toxicities are seen, the next 3 patients will be enrolled at the medium dose. If no dose limiting toxicities are seen in the medium dose, 6 additional patients will be enrolled on the high dose and will be evaluated for dose limiting toxicities. If in preparation of the vaccine insufficient RNA or dendritic cells are available to perform the required three injections at the assigned dose level or if the patient is withdrawn from the study the treatment position will remain open, i.e., no dose fractions will be given. Patients in whom only the minimum number of DCRCC-RNA can be produced to deliver one I.V. and one I.D. injection will be able to receive the vaccine, even if he or she is assigned to a higher dose level, but will be replaced in order to assess toxicity.
Data Analysis 1. To determine the short and long term toxicities associated with administration of DCRCC-RNA in patients with metastatic RCC. 2. To determine feasibility of DC vaccine generation according to the proportion of patients for whom sufficient cells are generated to provide treatment. 3. To determine the cellular immune response to administration of DCRCC-RNA. 4. To measure the clinical responses mediated by administration of DCRCC-RNA.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006431
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Johannes Vieweg, M.D.|