Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
- Determine the toxicity and tolerability of allogeneic peripheral blood stem cell
transplantation after a nonmyeloablative preparative regimen comprising anti-thymocyte
globulin, high-dose melphalan, and fludarabine in women with chemotherapy-refractory or
poor-prognosis metastatic adenocarcinoma of the breast.
- Determine the ability of this preparative regimen to facilitate long-term engraftment
of allogeneic stem cells and lymphocytes in these patients.
- Determine the response in measurable/evaluable disease and its temporal relationship to
the preparative chemotherapy used and to the onset of clinical graft-versus-host
disease (GVHD) in patients treated with this regimen.
- Determine the progression-free and overall survival of patients treated with this
- Determine the tumor response and its temporal relationship to administration of
high-dose chemotherapy and to the onset of GVHD in patients treated with this regimen.
- Determine the frequency and durability of the induction of full donor chimerism of
lymphocytes in patients treated with this regimen.
OUTLINE: This is a nonrandomized, pilot study.
- Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes
on days -8 to -4, anti-thymocyte globulin IV over 4 hours on days -7 to -4, and
high-dose melphalan IV over 30 minutes on days -3 and -2.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (and
then orally when tolerated) every 12 hours beginning on day -4 and tapered after day 42
(if no GVHD occurs) or after day 90 (if grade I acute GVHD occurs). Patients also
receive methotrexate IV on days 1, 3, and 6.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo
allogeneic PBSCT on day 0. Patients also receive filgrastim (G-CSF) IV or
subcutaneously beginning on day 0 and continuing until blood counts recover.
- Donor lymphocyte infusion (DLI): Patients who show disease progression or fail to
achieve full donor type T-cell chimerism (at least 90% donor derived T-cells) by the
90-day assessment posttransplantation, and have no evidence of active GVHD may receive
DLI. Patients who have unresponsive disease with no active GVHD receive subsequent DLIs
every 6-8 weeks.
Patients are followed at 1, 3, 6, 12, 18, 24, 30, and 36 months.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
Primary Purpose: Treatment
Edward D. Ball, MD
University of California, San Diego
United States: Federal Government
|Rebecca and John Moores UCSD Cancer Center||La Jolla, California 92093-0658|