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DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00085436
First received: June 10, 2004
Last updated: April 24, 2013
Last verified: October 2011

June 10, 2004
April 24, 2013
December 2003
October 2009   (final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00085436 on ClinicalTrials.gov Archive Site
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.
Not Provided
Not Provided
Not Provided
 
DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC
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)

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).

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

OUTLINE:

  • 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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Kidney Cancer
  • Biological: Aldesleukin,
    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 Names:
    • DC Vaccine
    • autologous tumor cell vaccine
  • Biological: 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
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.
Interventions:
  • Biological: Aldesleukin,
  • Biological: autologous tumor cell vaccine
  • Biological: recombinant interferon alfa
Schwaab T, Schwarzer A, Wolf B, Crocenzi TS, Seigne JD, Crosby NA, Cole BF, Fisher JL, Uhlenhake JC, Mellinger D, Foster C, Szczepiorkowski ZM, Webber SM, Schned AR, Harris RD, Barth RJ Jr, Heaney JA, Noelle RJ, Ernstoff MS. Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients. Clin Cancer Res. 2009 Aug 1;15(15):4986-92. Epub 2009 Jul 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
October 2009
October 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed metastatic renal cell carcinoma with measurable disease.
  • Tumor tissue available and properly stored for lysate preparation.
  • Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.
  • Karnofsky Performance Status ≥60%
  • Life expectancy ≥ twelve weeks
  • Adequate end organ function:
  • Hematological: ANC ≥ 1000cells/μL, platelets ≥ 75,000/μL, hemoglobin ≥ 8.5 g/dl
  • Liver: AST < 2 x ULN (upper limit of normal) unless due to metastases then < 5 x ULN, serum total bilirubin < 2 x ULN (except for patients with Gilbert's Syndrome)
  • Renal: serum creatinine < 2.0 x ULN.
  • Pulmonary: FEV1 > 2.0 liters or > 75% of predicted for height and age.
  • Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, or serious cardiac arrhythmias. Patients over 40 or have had previous myocardial infarction greater than 6 months prior to entry will be required to have a negative or low probability cardiac stress test for cardiac ischemia.
  • CNS: No history of brain metastases.
  • Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study.
  • Appropriate Contraception in both sexes

EXCLUSION CRITERIA:

  • Patients may have not have been treated previously with IL-2, IFNα or autologous vaccine.
  • Concomitant second malignancy except for non-melanoma skin cancer, and non- invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.
  • In patients with a prior history of invasive malignancy, less than five years in complete remission
  • Positive serology for HIV, hepatitis B or hepatitis C,
  • Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen.
  • Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 4 weeks must have passed since the last dose).
  • History of autoimmune disease.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00085436
CDR0000370794, R01CA095648, P30CA023108, DMS-0238, DMS-16090
No
Dartmouth-Hitchcock Medical Center
Dartmouth-Hitchcock Medical Center
National Cancer Institute (NCI)
Study Chair: Marc S. Ernstoff, MD Norris Cotton Cancer Center
Dartmouth-Hitchcock Medical Center
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP