Pentostatin Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Kidney Cancer

OBJECTIVES:

• Determine the duration and efficiency of hematopoietic and immunologic engraftment in patients with advanced renal cell carcinoma treated with pentostatin followed by related allogeneic stem cell transplantation.
• Determine the hematologic and non-hematologic toxic effects of this regimen in these patients.
• Determine the incidence and severity of graft-versus-host disease in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of pentostatin.

• Phase I: Patients receive pentostatin IV on days -7, -5, and -3 followed by allogeneic stem cell transplantation on day 0. Beginning on day 1, patients receive filgrastim (G-CSF) IV over 1 hour or subcutaneously daily until blood counts recover. As graft-versus-host disease prophylaxis, patients receive cyclosporine IV continuously until stem cell engraftment and then orally with gradual tapering.

Cohorts of 3 to 6 patients receive escalating doses of pentostatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive treatment as in phase I at the MTD for pentostatin. Patients are followed weekly for 60 days and then monthly for 10 months.

PROJECTED ACCRUAL: A total of 24 patients (12 per phase) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced renal cell cancer
• No bone metastases
• No CNS disease
• Must have an allogeneic donor available

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-1

Life expectancy:

• 3 to 6 months

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Complete blood count normal

Hepatic:

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• Transaminases no greater than 4 times ULN
• No evidence of portal hypertension

Renal:

• Creatinine no greater than 2.0 mg/dL
• No uncontrolled hypercalcemia

Cardiovascular:

• No New York Heart Association class 3 or 4 heart disease

Pulmonary:

• DLCO at least 40% of predicted

Other:

• No severe functional neurological impairment
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No more than 1 prior biologic therapy

Chemotherapy:

• No more than 6 months of prior chemotherapy

Endocrine therapy:

• At least 1 year since prior steroids

Radiotherapy:

• Not specified

Surgery:

• Not specified