Allogeneic Transplantation Using Mini-Conditioning for Treatment of Stage IV Breast Cancer

• Tumor response in women with stage IV breast cancer who achieve PR after a mini-conditioning regimen comprising fludarabine and cyclophosphamide, followed by PBSCT and DLI. [ Time Frame: Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. ] [ Designated as safety issue: No ]
  

Biological: therapeutic allogeneic lymphocytes
Beginning on day 120 after PBSC transplantation, eligible patients receive unmobilized donor lymphocyte infusion (DLI) over 15-30 minutes. Treatment continues monthly for a total of 3 DLIs in the absence of grade III or IV graft versus host disease or marrow aplasia.
Drug: cyclophosphamide
4-10 weeks after completion of salvage chemotherapy, patients achieving complete or partial remission or stable disease receive mini-conditioning comprised of cyclophosphamide IV over 2 hours on days -3 and -2.
Drug: docetaxel
Docetaxel IV over 1 hour. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: doxorubicin hydrochloride
Doxorubicin IV over several minutes on day 1. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: fludarabine phosphate
4-10 weeks after completion of salvage chemotherapy, patients achieving complete or partial remission or stable disease receive mini-conditioning comprised of fludarabine IV over 30 minutes on days -8 to -4.
Procedure: peripheral blood stem cell transplantation
Filgrastim (G-CSF) and sargramostim (GM-CSF) mobilized allogeneic peripheral blood stem cells (PBSC) IV on day 0.

OBJECTIVES: I. Determine the tumor response in women with stage IV breast cancer who achieve partial remission after a mini-conditioning regimen comprising fludarabine and cyclophosphamide, followed by allogeneic peripheral blood stem cell transplantation (PBSCT), and donor lymphocyte infusion (DLI). II. Determine the progression free survival in patients who achieve complete remission after this treatment regimen. III. Determine whether DLI exerts graft versus tumor effect in these patients. IV. Determine the acute and delayed toxicities of this regimen in these patients. V. Determine the rates of durable hematologic engraftment in patients treated with this regimen. VI. Determine the incidence and severity of acute and chronic graft versus host disease in patients treated with this regimen. VII. Determine the extent of chimerism in patients treated with this nonmyeloablative conditioning regimen. VIII. Determine the rate and quality of immune reconstitution in patients treated with this regimen. IX. Determine the event free and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients receive salvage chemotherapy comprised of docetaxel IV over 1 hour and doxorubicin IV over several minutes on day 1. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning within 4-10 weeks after completion of salvage chemotherapy, patients achieving complete or partial remission or stable disease receive mini-conditioning comprised of fludarabine IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then receive filgrastim (G-CSF) and sargramostim (GM-CSF) mobilized allogeneic peripheral blood stem cells (PBSC) IV on day 0. Beginning on day 120 after PBSC transplantation, eligible patients receive unmobilized donor lymphocyte infusion (DLI) over 15-30 minutes. Treatment continues monthly for a total of 3 DLIs in the absence of grade III or IV graft versus host disease or marrow aplasia. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study.