Allogeneic Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer

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.

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