Adoptive Immunotherapy, Aldesleukin, and Zoledronate in Treating Patients With Stage IV Kidney Cancer and Lung Metastases

Study Overview
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Brief Summary
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RATIONALE: Cellular adoptive immunotherapy uses a person's white blood cells that are treated in the laboratory to stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may help the laboratory-treated white blood cells stay in the body longer. Drugs used in chemotherapy, such as zoledronic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cellular adoptive immunotherapy together with interleukin-2 and zoledronic acid may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving cellular adoptive immunotherapy together with aldesleukin and zoledronic acid and to see how well it works in treating patients with stage IV kidney cancer and lung metastases.

Detailed Description
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OBJECTIVES: Determine the safety of adoptive immunotherapy comprising 2-methyl-3-butenyl-1-pyrophosphate-stimulated gamma delta (gd) T cells, zoledronate, and IL-2 after nephrectomy, especially with regard to the incidence and frequency of adverse events. Determine the duration of in vivo persistence of the transferred gd T cells in patients. Determine the doubling time of tumor growth before and after adoptive immunotherapy. Determine the tumor-size reducing effect of adoptive immunotherapy based on the Best Overall Response Chart. OUTLINE: Patients undergo leukapheresis for the harvest of peripheral blood mononuclear cells (PBMCs). PBMCs are stimulated with 2-methyl-3-butenyl-1-pyrophosphate and aldesleukin for 11 days. Patients then receive the expanded Gamma Delta T cells, aldesleukin, and zoledronic acid once a month for 6 months. After completion of study treatment, patients are followed for up to 1 month.

Official Title
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Phase I/II Study of Adoptive Immunotherapy Comprising Pyrophosphomonoester Antigen-stimulated T Cells, IL-2, and Nitrogen-containing Bisphosphonates in Patients With Stage IV Renal Cell Carcinoma

Conditions
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Kidney Cancer, Metastatic Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Biological: therapeutic autologous lymphocytes
* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal carcinoma Stage IV disease with lung metastases Bidimensionally measurable lung metastases by CT scan Meets 1 or more of the following criteria: No change in disease status or progressive disease after prior aldesleukin administration for 3 months or more Lung metastases after treatment with prior nephrectomy Patients with clear cell renal carcinoma must have undergone nephrectomy prior to study entry Patients with progression of metastatic lung cancer after nephrectomy also must have received interferon alfa for 3 months or more (prior to study entry) PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 6 months Leukocyte count ≥ 3,000/mm³ ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Serum bilirubin ≤ 1.5 mg/dL AST/ALT ≤ 2.5 times normal Serum creatinine ≤ 1.7 mg/dL LDH ≤ 1.5 times normal Not pregnant nor nursing Negative pregnancy test Fertile patients must use effective contraception No active infection with hepatitis virus or HIV No poorly controlled heart failure or arrhythmia No hypercalcemia that require medication No C-reactive protein with an infectious disease that requires medication PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior chemotherapy, radiation therapy, or biologic therapy No prior bone marrow transplantation or organ transplantation No concurrent steroid therapy No concurrent antidepressant therapy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: therapeutic autologous lymphocytes|nan|
|Drug: zoledronic acid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events based on NCI-CTCAE version 3.0 |  |  | 
| Proportion of gd T-cells in peripheral blood |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary doubling time of tumor growth |  |  | 
| Overall response |  |  | 

 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, clear cell renal cell carcinoma, lung metastases