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

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.