Radiolabeled Monoclonal Antibody Therapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Breast Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 labeled, humanized monoclonal antibody BrE-3 when given in combination with indium In 111 labeled, humanized monoclonal antibody BrE-3 followed by autologous bone marrow or peripheral blood stem cell transplantation in patients with metastatic breast cancer.
• Determine hematopoietic engraftment in these patients treated with this regimen.
• Determine the ability of indium In 111 labeled, humanized monoclonal antibody BrE-3 to image metastatic disease in these patients.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the preliminary antitumor response in these patients treated with this regimen.

OUTLINE: This is a dose escalation study of yttrium Y 90 labeled, humanized monoclonal antibody BrE-3 (Y90 huMOAB BrE-3).

Patients receive Y90 huMOAB BrE-3 and indium In 111 labeled, humanized monoclonal antibody BrE-3 IV over 1-2 hours on day -14. Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 0 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of Y90 huMOAB BrE-3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities.

Patients are followed every 3-4 months for 1 year and then at least annually thereafter.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic breast cancer

• BrE-3 positive
• Relapsed or refractory disease with tumor progression after effective therapy allowed
• Measurable or evaluable disease
• Received at least one prior chemotherapy regimen for metastatic disease and have at least one of the following:

• Chemotherapy refractory liver metastases more than 2 cm
• Multiple non-resectable liver metastases
• Brain metastases
• Prior high-dose chemotherapy
• Relapse within prior radiotherapy field
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• Over 18

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm3
• Absolute neutrophil count greater than 1,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin less than 2 times normal
• SGOT/SGPT less than 2 times normal

Renal:

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• LVEF greater than 45% by MUGA scan

Pulmonary:

• DLCO and FEV 1.0 greater than 60% predicted

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity to E. coli derived proteins
• No other comorbid condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior high-dose chemotherapy with autologous peripheral blood stem cell transplantation

Chemotherapy:

• See Disease Characteristics
• See Biologic therapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified

Other:

• Recovered from prior therapy