Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Unresectable Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have metastatic or unresectable kidney cancer.

Detailed Description
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OBJECTIVES: Determine the overall response rate and overall and disease-free survival of patients with unresectable or metastatic renal cell cancer treated with fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation. Determine the toxicity and treatment-related mortality of this regimen in these patients. Determine the percentage of donor chimerism in patients treated with this regimen.

Official Title
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Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: A Phase II Study

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: filgrastim
* Biological: therapeutic allogeneic lymphocytes
* Drug: cyclophosphamide
* Drug: fludarabine phosphate
* Drug: methotrexate
* Drug: tacrolimus
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma (RCC) Clear cell or papillary RCC Granular tumors with sarcomatoid features No purely sarcomatoid RCC, chromophobic RCC, or oncocytoma No transitional cell carcinoma of the renal pelvis and collecting systems Metastatic or unresectable disease At least 1 measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are not considered measurable: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Primary bladder masses Progressive disease after interferon alfa and/or interleukin-2 for metastatic RCC OR intolerance to these therapies No prior or concurrent CNS metastases Negative MRI of the brain within the past 28 days Must have HLA-identical (6/6) sibling donor PATIENT CHARACTERISTICS: Age: 60 and under Performance status: ECOG 0-1 Life expectancy: More than 6 months Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST no greater than 3 times ULN Renal: Creatinine clearance at least 40 mL/min Cardiovascular: LVEF at least 45% by MUGA or echocardiogram Pulmonary: DLCO greater than 40% of predicted (corrected for hemoglobin level) No symptomatic pulmonary disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No known hypersensitivity to E. coli-derived products No uncontrolled diabetes mellitus No active serious infection No other concurrent malignancy except non-melanoma skin cancer or other malignancy that has less than a 30% risk of relapse after completion of therapy PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent sargramostim (GM-CSF) Concurrent epoetin alfa allowed Chemotherapy: No other concurrent chemotherapy Endocrine therapy: At least 28 days since prior hormonal therapy (e.g., megestrol, corticosteroids, or anti-estrogen therapy) Concurrent steroids allowed for adrenal failure, graft-versus-host disease, or other nondisease-related conditions (e.g., insulin for diabetes) Radiotherapy: At least 14 days since prior radiotherapy Surgery: At least 14 days since prior surgery Other: At least 28 days since prior systemic therapy for RCC Recovered from prior therapy

Ages Eligible for Study
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Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy + stem cell transplantation<br>Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1-2 hours on days -4 and -3. Allogeneic peripheral blood stem cells are infused on day 0. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising oral tacrolimus twice daily on days -1 to 90 and methotrexate IV on days 1, 3, and 6. After day 120, patients with persistent disease and no signs of active GVHD may receive donor lymphocyte infusion (DLI). DLI may be repeated every 8 weeks for a total of 2 infusions. Patients are followed every 2 months for 1 year and then every 6 months for 4 years OR every 2 months for 6 months and then every 6 months for 4.5 years if patient receives DLI. | Biological: filgrastim<br> <br> Biological: therapeutic allogeneic lymphocytes<br> <br> Drug: cyclophosphamide<br> <br> Drug: fludarabine phosphate<br> <br> Drug: methotrexate<br> <br> Drug: tacrolimus<br> <br> Procedure: peripheral blood stem cell transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 
| Disease-free survival |  | Up to 5 years | 
| Treatment-related mortality |  | Up to 5 years | 
| Percentage of donor chimerism in patients treated |  | Up to 5 years | 

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