Allogeneic Transplantation Using Mini-Conditioning for Treatment of Stage IV Breast Cancer
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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Hillard M. Lazarus, MD
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
United States: Federal Government
|Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|