Allogeneic Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: This phase II trial is studying how well allogeneic stem cell transplant works in treating patients with metastatic kidney cancer.

Detailed Description
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OBJECTIVES: Determine the 18-month survival rate of patients with metastatic renal cell carcinoma treated with allogeneic stem cell transplantation. Determine the objective rate of response of patients treated with this regimen. Determine post-transplant immunological reactions and recuperation of patients treated with this regimen. Determine the antitumoral activity of this regimen in these patients. OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups based on availability of a compatible family member for stem cell transplantation. Group I: Patients with a compatible family donor receive conditioning chemotherapy comprising cyclophosphamide IV over 2 hours on days -7 and -6 and fludarabine IV once daily on days -5 to -1. Patients undergo filgrastim (G-CSF)-mobilized allogeneic stem cell transplantation on day 0. Patients also receive immunosuppression therapy with cyclosporine beginning on day -2. Patients who have persistent or progressive disease, mixed chimerism, and no evidence of grade 2 or greater graft-vs-host disease, and have been off immunosuppression therapy for 1-2 weeks receive donor lymphocyte infusion on days 7 and 21. Group II: Patients without a compatible family donor receive treatment (immunotherapy, vaccination therapy, or chemotherapy) at the discretion of the treating physician. Patients are followed every 3 months for 5 years. PROJECTED ACCRUAL: A total of 170 patients (60 patients for group I and 110 patients for group II) will be accrued for this study within 3 years.

Official Title
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Phase II Trial in Intrafamilial Allogeneic Cell Transplant in Patients With Metastatic Kidney Cancer

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: therapeutic allogeneic lymphocytes
* Drug: cyclophosphamide
* Drug: cyclosporine
* Drug: fludarabine phosphate
* Procedure: allogeneic bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic renal cell carcinoma No sarcomatoid, pure papillary, or Bellini renal cell cancer Measurable and/or evaluable disease Disease progression after at least 1 immunotherapy regimen for metastatic disease Localized metastases allowed provided the following are true: At least 3 months since prior treatment for metastases Not considered likely to influence outcome of transplantation No brain metastases unless treated surgically or radiologically and MRI normal Sufficiently healthy, HLA-compatible family member must be available as donor for patients undergoing stem cell transplantation PATIENT CHARACTERISTICS: Age 18 to 65 Performance status ECOG 0-1 Life expectancy More than 6 months Hematopoietic Platelet count at least 100,000/mm^3 Hepatic Transaminases less than 1.5 times upper limit of normal (ULN)* Bilirubin less than 1.5 times ULN* NOTE: *Unless due to Gilbert's disease Renal No renal insufficiency Calcium less than 10.4 mg/dL Creatinine clearance greater than 50 mL/min Cardiovascular Ejection fraction greater than 50% Pulmonary No DLCO that would preclude fludarabine or busulfan therapy Other Not pregnant or nursing Fertile patients must use effective contraception No physical obstacle to receiving study treatment No known autoimmune disease No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No uncontrolled bacterial, viral, or fungal infection No prior or concurrent psychiatric disease HIV negative HTLV1 negative PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy No tolerance to fludarabine and busulfan Endocrine therapy No concurrent corticosteroids Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allograft (compatible family member)<br> | Biological: therapeutic allogeneic lymphocytes<br> <br> Drug: cyclophosphamide<br> <br> Drug: cyclosporine<br> <br> Drug: fludarabine phosphate<br> <br> Procedure: allogeneic bone marrow transplantation<br> <br> Procedure: peripheral blood stem cell transplantation<br> <br> |
| Other: Allograft (compatible non-family member)<br> | Procedure: allogeneic bone marrow transplantation<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 |
| --- | --- | --- |
| Survival rate at 18 months |  |  | 
| Objective rate of response |  |  | 
| Post-transplant immunological reactions and recuperation |  |  | 
| Antitumoral activity |  |  | 

 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