dc vaccine combined with il-2 and ifnα-2a in treating patients with mrcc

Conditions: Kidney Cancer

Summary: 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.

Eligibility criteria:
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.

Keywords: recurrent renal cell cancer stage iv renal cell cancer