DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC
RATIONALE: Vaccines made from a patient's dendritic cells and tumor cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's lymphocytes to kill kidney cancer cells. Interferon alfa may interfere with the growth of cancer cells. Combining vaccine therapy with interleukin-2 and interferon alfa may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving vaccine therapy together with interleukin-2 and interferon alfa works in treating patients with metastatic renal cell carcinoma (kidney cancer).
Biological: autologous tumor cell vaccine
Biological: recombinant interferon alfa
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Of Autologous Tumor/DC Vaccine (DC Vaccine) Combined With Interleukin-2 (IL-2) And Interferon-α-2a (IFNα-2a) In Patients With Metastatic Renal Cell Carcinoma (RCC)|
- Clinical Response as Measured by RECIST Monthly and Then Every 2-3 Months [ Time Frame: If 4 or fewer responses are observed in the first stage, the trial will be stopped ] [ Designated as safety issue: No ]A total of 18 evaluable patients will be accrued in the first stage. If 4 or fewer responses are observed in the first stage, the trial will be stopped early, otherwise an additional 15 evaluable patients will be accrued for a total of 33 evaluable patients. If 11 or more responses are observed among the 33 patients, the experimental regimen will be considered for further study, otherwise it will be rejected. The trial will not proceed to the second stage unless at least 5 responses are observed in the first stage.
- Immunity as Measured by T-cell and Antibody Responses to the Tumor [ Time Frame: monthly for 5 months ] [ Designated as safety issue: No ]All patients receiving at least one week of treatment and have at least two time points available for assessment of immune parameters will be include in the evaluation of immune status.
|Study Start Date:||December 2003|
|Study Completion Date:||October 2009|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
Experimental: Vaccine, Aldesleukin-2, Interferon-a
All patients will be treated with autologous tumor cell vaccine administered into inguinal lymph nodes via ultrasound guidance in addition to systemic IL-2 and recombinant interferon alfa. Two cycles of induction IL-2/IFNα-2a followed by 3 cycles of maintenance IL-2 + IFNα-2a.
Recombinant human interleukin-2 (Proleukin, Chiron Therapeutics) will be administered as a five day (120 hr) continuous intravenous infusion at a dose of 18x106 IU per square meter of body surface area per day as per the Negrier regimen (21). The treatment schedule consists of two induction cycles and three maintenance cycles. Each induction cycle consists of two five-day courses of interleukin-2 infusion separated by a nine-day break. Each maintenance cycle consists of a five-day infusion followed by 23-day rest period of no therapy.
Other Name: IL-2 (Proleukin®, Chiron)Biological: autologous tumor cell vaccine
we will administer 1 X 107 DC cells. The autologous tumor cell vaccine (1 X 107 cells/1cc) in lactated ringers solution and injected into one (or two if clinically necessary) inguinal lymph nodes under ultrasound guidance. Each cycle of DC vaccine will be administered alternately in the right and left inguinal lymph nodes.
Other Name: DC VaccineBiological: recombinant interferon alfa
Recombinant human interferon alfa-2a (Roferon, Roche), at a dose of 6 million IU per day three times a week subcutaneously will be given during the two interleukin-2 induction cycles and during each interleukin-2 maintenance cycle
Other Name: interferon alfa-2a; Roferon
- Determine the clinical response rate in patients with metastatic renal cell carcinoma treated with autologous dendritic cells (DC) loaded with autologous tumor lysate (DC vaccine) in combination with interleukin-2 and interferon-alfa.
- Determine the toxicity of this regimen in these patients.
- Determine, within relevant immune pathways, the treatment-related, tumor-specific immune response in patients treated with this regimen.
- Correlate tumor-specific immune response with objective clinical response in patients treated with this regimen.
- Induction therapy: Patients undergo leukapheresis on day -9. Patients receive autologous dendritic cells (DC) loaded with autologous tumor lysate (DC vaccine) by intranodal injection on days 0 and 14; interleukin-2 (IL-2) IV continuously on days 1-5 and 15-19; and interferon-alfa (IFN-α) subcutaneously (SC) once daily on days 1, 3, 5, 15, 17, and 19.
- Maintenance therapy: Patients undergo leukapheresis on days 33, 61, and 89. Patients receive DC vaccine by intranodal injection on days 42, 70, and 98; IL-2 IV continuously on days 43-47, 71-75, and 99-103; and IFN-α SC once daily on days 43, 45, 47, 71, 73, 75, 99, 101, and 103.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00085436
|United States, New Hampshire|
|Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756-0002|
|Study Chair:||Marc S. Ernstoff, MD||Norris Cotton Cancer Center|