Fludarabine and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Metastatic Kidney Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine together with total-body irradiation works in treating patients who are undergoing a donor stem cell transplant for metastatic kidney cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Determine the efficacy of nonmyeloablative conditioning comprising fludarabine and total-body irradiation followed by allogeneic hematopoietic stem cell transplantation, in terms of 6-month and 12-month response rate, in patients with unresectable metastatic renal cell carcinoma. OUTLINE: Nonmyeloablative conditioning regimen: Patients receive fludarabine IV on days -4 to -2 and total-body irradiation (TBI) on day 0. Allogeneic hematopoietic stem cell transplantation (AHSCT): After TBI, patients undergo AHSCT on day 0. Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper until day 81. Patients also receive oral mycophenolate mofetil twice daily on days 0-27 (if patient has a related donor) OR three times daily on days 0-29 and then twice daily on days 30-149 followed by additional tapering until day 180 (if patient has an unrelated donor). PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Official Title
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Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Metastatic Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: cyclosporine
* Drug: fludarabine phosphate
* Drug: mycophenolate mofetil
* Procedure: allogeneic bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma, including 1 of the following subtypes: Clear cell Papillary Medullary Metastatic disease Not amenable to curative surgery No CNS metastases PATIENT CHARACTERISTICS: Performance status Karnofsky 70-100% Life expectancy More than 6 months Hematopoietic Not specified Hepatic Bilirubin < 2 times upper limit of normal (ULN) AST or ALT < 4 times ULN Renal Creatinine clearance > 50 mL/min Cardiovascular LVEF > 35% No symptomatic congestive heart failure Pulmonary DLCO > 40% of predicted OR Total lung capacity or FEV_1 > 30% of predicted PRIOR CONCURRENT THERAPY: Biologic therapy More than 30 days since prior biologic therapy Chemotherapy More than 30 days since prior chemotherapy Radiotherapy More than 30 days since prior radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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

| Intervention/Treatment |
| --- |
|Drug: cyclosporine|nan|
|Drug: fludarabine phosphate|nan|
|Drug: mycophenolate mofetil|nan|
|Procedure: allogeneic bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial response) at 6 and 12 months after transplantation |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of graft-vs-host-disease by Glucksburg Scale after transplantation for up to 5 years |  |  | 
| Incidence of graft rejection based on donor chimerims after transplantation for up to 5 years |  |  | 
| Non-relapse mortality as assessed by Kaplan-Meier after transplantation for up to 5 years |  |  | 
| Disease-free survival as assessed by Kaplan-Meier after transplantation for up to 5 years |  |  | 
| Overall survival as assessed by Kaplan-Meier after transplantation for up to 5 years |  |  | 
| Toxicity as measured by CTC AE v 3.0 100 days after transplantation |  |  | 

 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