Vaccine Therapy With or Without Fludarabine in Treating Patients With Stage IV Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's tumor cells and white blood cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with fludarabine may kill more tumor cells. PURPOSE: This randomized phase II trial is studying vaccine therapy and fludarabine to see how well they work compared to vaccine therapy alone in treating patients with stage IV kidney cancer.

Detailed Description
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OBJECTIVES: Primary Compare the safety of vaccination comprising autologous dendritic cells loaded with autologous tumor lysate and keyhole limpet hemocyanin with vs without non-myeloablative fludarabine in patients with stage IV renal cell carcinoma. Compare, preliminarily, the efficacy of these regimens in these patients. Compare the overall survival of patients treated with these regimens. Secondary Determine whether this vaccine induces tumor-reactive peripheral T-cell responses or delayed-type hypersensitivity in these patients. OUTLINE: This is a pilot, randomized study. Patients are randomized to 1 of 2 treatment arms. All patients undergo surgery to remove tumor at metastatic sites to generate autologous tumor lysate. Patients then undergo leukapheresis to obtain peripheral blood mononuclear cells for the generation of dendritic cells (DC). The DC are then exposed to autologous tumor lysate and keyhole limpet hemocyanin (KLH). Arm I: Three weeks after leukapheresis, patients receive vaccination comprising DC loaded with autologous tumor lysate and KLH (DC vaccine) intradermally once every 14 days for a total of 4 injections in the absence of disease progression or unacceptable toxicity. Arm II: Two weeks after leukapheresis, patients receive fludarabine IV over 15-30 minutes once daily for 3 days. Beginning approximately 5 weeks after leukapheresis, patients also receive DC vaccine as in arm I. Patients are followed at 1, 3, and 7-9 weeks, at 4, 6, 9, and 12 months, and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 28 patients (14 per treatment arm) will be accrued for this study within 2-3 years.

Official Title
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A Phase II Pilot Study of Tumor-Loaded Dendritic Cells Alone or Following a Non-Myeloablative Conditioning Regimen in Patients With Metastatic Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: autologous tumor cell vaccine
* Biological: keyhole limpet hemocyanin
* Biological: therapeutic autologous dendritic cells
* Drug: fludarabine phosphate
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma Stage IV disease Received no benefit from standard therapy OR ineligible for standard therapy OR declined standard therapy At least 1 site of metastatic disease that can be surgically removed AND at least 1 site of metastatic disease than can remain in the patient (indicator lesion) after surgery Total volume of the site or sites of disease to be surgically removed must be > 2.0 cm^3 Unidimensionally measurable disease At least 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No brain metastasis PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy More than 6 months Hematopoietic WBC ≥ 3,000/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 10 g/dL Hepatic SGPT and SGOT ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Hepatitis C antibody negative Hepatitis B surface antigen negative Renal Creatinine ≤ 1.5 times ULN Creatinine clearance > 40 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Immunologic Coomb's test negative HIV-1 and -2 negative No active infection No unexplained fever (temperature > 100.5° F or 38.1°C) No lymphocytopenia No hypogammaglobulinemia No autoimmune disease or other immunocompromising condition that would preclude study participation No history of impaired immune response No history of tuberculosis OR positive PPD skin test No history of allergic reaction attributed to compounds of similar biological composition to study vaccine No history of allergic reaction to antibiotics Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study participation No psychiatric illness or social situation that would preclude study participation No other malignancy within the past 5 years except resected basal cell carcinoma or carcinoma in situ of the cervix No other concurrent illness PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior immunotherapy Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) Endocrine therapy At least 4 weeks since prior steroid therapy or steroid-containing compounds At least 2 weeks since prior topical or inhaled steroids Radiotherapy More than 4 weeks since prior radiotherapy Surgery See Disease Characteristics Other More than 4 weeks since prior investigational agents More than 1 week since prior antibiotics No concurrent renal dialysis No concurrent anticoagulants No other concurrent anticancer agents or therapies No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: autologous tumor cell vaccine|nan|
|Biological: keyhole limpet hemocyanin|nan|
|Biological: therapeutic autologous dendritic cells|nan|
|Drug: fludarabine phosphate|nan|
|Procedure: conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by NCI common toxicity table at completion of study |  |  | 
| Response as measured by RECIST guidelines and the Kaplan-Meier method at 5 years |  |  | 
| Survival as measured by the Kaplan-Meier method at 5 years |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent renal cell cancer, stage IV renal cell cancer