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

Phase 2

Completed

Interventions: Biological: Aldesleukin,
Biological: autologous tumor cell vaccine
Biological: recombinant interferon alfa

Brief 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).

Detailed Description: 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.

Recruitment & Eligibility

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.

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Vaccine, Aldesleukin-2, Interferon-a	autologous tumor cell vaccine	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.
Vaccine, Aldesleukin-2, Interferon-a	Aldesleukin,	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.
Vaccine, Aldesleukin-2, Interferon-a	recombinant interferon alfa	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.

Primary Outcome Measures

Name	Time	Method
Clinical Response as Measured by RECIST	monthly, then every 2-3 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Name	Time	Method
Immunity as Measured by T-cell and Antibody Responses to the Tumor	monthly for 5 months	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.