Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00074269|
Recruitment Status : Terminated (Terminated early due to poor enrollment)
First Posted : December 11, 2003
Results First Posted : November 24, 2014
Last Update Posted : December 10, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||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||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer|
|Study Start Date :||July 2003|
|Actual Primary Completion Date :||March 2008|
|Actual Study Completion Date :||March 2008|
|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|
- Adverse Events Rate [ Time Frame: 5 years post transplant ]
- Facilitation of Long-term Engraftment [ Time Frame: post treatment ]
- Incidence and Severity of Acute and Chronic Graft-versus-host Disease (GVHD) [ Time Frame: post treatment ]
- Progression-free Survival [ Time Frame: post treatment ]
- Overall Survival [ Time Frame: post treatment ]
- 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 ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|