Allogeneic Peripheral Stem Cell Transplant After Antithymocyte Globulin, High-Dose Melphalan, and Fludarabine in Treating Women With Metastatic Adenocarcinoma of the Breast
RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin, cyclosporine, and methotrexate before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well antithymocyte globulin, high-dose melphalan, fludarabine, and allogeneic peripheral stem cell transplant work in treating patients with metastatic adenocarcinoma of the breast.
Biological: anti-thymocyte globulin
Biological: graft-versus-tumor induction therapy
Biological: therapeutic allogeneic lymphocytes
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer|
- Toxicity [ Time Frame: period of the treatment ] [ Designated as safety issue: Yes ]
- Facilitation of long-term engraftment [ Time Frame: post treatment ] [ Designated as safety issue: No ]
- Incidence and severity of acute and chronic graft-versus-host disease (GVHD) [ Time Frame: post treatment ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: post treatment ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: post treatment ] [ Designated as safety issue: No ]
- Response (partial and complete) as measured at 1, 3, 6, and 12 months post allografting and within 1 week after the onset of documented GVHD if > 1 month separates any of the response evaluation timepoints [ Time Frame: post treatment ] [ Designated as safety issue: No ]
- Frequency and durability of the induction of full donor chimerism of lymphocytes as measured at 1, 3, 6, and 12 months post allografting [ Time Frame: post treatment ] [ Designated as safety issue: No ]
|Study Start Date:||July 2003|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
|Experimental: treatment||Biological: anti-thymocyte globulin Biological: filgrastim Biological: graft-versus-tumor induction therapy Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Procedure: peripheral blood stem cell transplantation|
- 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 regimen.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00074269
|United States, California|
|Rebecca and John Moores UCSD Cancer Center|
|La Jolla, California, United States, 92093-0658|
|Principal Investigator:||Edward D. Ball, MD||University of California, San Diego|