Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Melanoma or 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 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 plus peripheral stem cell transplantation in treating patients who have metastatic kidney cancer or melanoma.

Detailed Description
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OBJECTIVES: Evaluate the safety of nonmyeloablative chemotherapy followed by allogeneic peripheral blood stem cell transplantation in patients with metastatic renal cell carcinoma or melanoma. Determine the incidence and severity of all adverse events related to this treatment regimen in this patient population. Determine the efficacy of this treatment regimen in terms of tumor regression, response duration, progression free survival, and overall survival in these patients. Measure the resulting chimerism and immune reconstitution in these patients after this treatment regimen and correlate with clinical response. OUTLINE: Patients receive fludarabine IV over 30 minutes on days -8 through -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Immediately following each daily donor leukapheresis, patients receive allogeneic peripheral blood stem cells (PBSC) IV over 15 minutes beginning on day 0 and continuing until the target cells are collected. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover. If no graft versus host disease has developed within 4 weeks of allogeneic PBSC transplantation, patients with disease progression or recurrence who have residual donor hematopoiesis on chimerism analysis may receive donor T lymphocytes IV over 30 minutes. Patients may receive an additional course of donor T lymphocytes at the investigator's discretion. Patients are followed at days 30 and 100, and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 10-38 patients will be accrued for this study within 2.5 years.

Official Title
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Allogeneic Stem Cell Transplantation of Renal Cell Cancer and Metastatic Melanoma After Non-Myeloablative Chemotherapy

Conditions
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Kidney Cancer, Melanoma (Skin)

Intervention / Treatment
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* Biological: filgrastim
* Biological: therapeutic allogeneic lymphocytes
* Drug: cyclophosphamide
* Drug: fludarabine phosphate
* 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 or melanoma that is not potentially curable by surgery Evaluable disease or bidimensionally measurable disease on physical examination, chest x-ray, CT scan, or MRI Measurable disease by radiography must be reproducible Bony disease or effusions not measurable No active CNS disease currently receiving radiotherapy or steroids No effusion or ascites of more than 1 liter prior to drainage HLA 5/6 or 6/6 matched sibling donor available No known hypersensitivity to E. coli derived products No active infection No health condition that would preclude donation PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: CALGB 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 g/dL No active hepatitis Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance greater than 50 mL/min Cardiovascular: LVEF at least 50% Pulmonary: DLCO at least 50% of predicted Other: No active infection HIV negative No psychological problem that would preclude study compliance No known hypersensitivity to E. coli derived products Not pregnant or nursing Negative pregnancy test PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior systemic chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Fludarabine 30 mg/m2/d x S days IVPB in 100 cc NS over 30 minutes on day -8, -7, -6, -S, and -4. Cyclophosphamide 2 gm/m2/d x 2 days IVPB in SOO cc DS W over I hour on day -3 and day-2. G-CSF (Neupogen®) administration 480 f!gld subcutaneously starting on day +5 (or first day of neutropenia if earlier)and continued until an ANC of 0.5 x 109/L is maintained for 3 consecutive days. | Biological: filgrastim<br> <br> Biological: therapeutic allogeneic lymphocytes<br> <br> Drug: cyclophosphamide<br> <br> Drug: fludarabine phosphate<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 |
| --- | --- | --- |
| Complete Response Rate |  | 3 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, stage IV melanoma, recurrent melanoma