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.

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.