Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Melanoma or Metastatic Kidney Cancer

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.

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