Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Metastatic Breast Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 6/2/2018 |
| Start Date: | July 2003 |
| End Date: | March 2008 |
Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
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.
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.
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Primary
- 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.
Secondary
- 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.
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the breast
- Metastatic disease
- Meets 1 of the following criteria:
- Chemotherapy-unresponsive disease defined as 1 of the following:
- Less than a partial response to 2 consecutive chemotherapy regimens that
included an anthracycline and a taxane in combination or succession
- Progression of disease during or within 3 months of completion of a taxane,
anthracycline, or platinol-based regimen
- Histologically confirmed tumor involvement on bone marrow biopsy
- Measurable or evaluable disease* defined as the following:
- Bidimensionally reproducible measurable mass by physical examination,
ultrasonography, radiography, CT scan, or MRI
- Evaluable lesions apparent on clinical exam, x-ray, CT scan, or MRI which do not
fit the criteria for measurability (e.g., ill-defined post-surgical masses or
masses assessable in 1 dimension only)
- Elevation of biological markers (e.g., CA 27.29) is considered evaluable
disease NOTE: *Bone lesions or pleural or peritoneal effusion alone are not
considered measurable or evaluable disease
- Appropriate candidate for allogeneic stem cell transplantation
- No active CNS metastases
- Available HLA-identical sibling donor
- 6/6 antigen match
- Donor CD34 cells at least 2 times 10^6/kg recipient weight
- Hormone receptor status:
- Estrogen receptor negative or positive
- Estrogen receptor positive tumors must demonstrate progression on at least 1
hormonal manipulation
PATIENT CHARACTERISTICS:
Age
- 18 to 60
Sex
- Female
Menopausal status
- Not specified
Performance status
- Karnofsky 70-100% OR
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- WBC at least 1,500/mm^3
- Platelet count at least 30,000/mm^3
Hepatic
- Bilirubin less than 3 times normal*
- AST and ALT less than 3 times normal* NOTE: *Unless abnormality due to malignancy
Renal
- Creatinine no greater than 1.6 mg/dL
Cardiovascular
- LVEF greater than 40% by echocardiography or MUGA
- No myocardial infarction within the past 6 months
Pulmonary
- DLCO greater than 40% of predicted
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No serious localized or systemic infection
- No hypersensitivity to E. coli-derived products
- No history of non-breast malignant disease within the past 5 years except completely
excised nonmelanoma skin cancer or carcinoma in situ of the cervix
- No chronic inflammatory disorder requiring concurrent glucocorticosteroids or other
immunosuppressive medication
- No psychological condition or social situation that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- No concurrent glucocorticoids
Radiotherapy
- No prior radiotherapy to an indicator lesion unless the lesion shows evidence of
progression after discontinuation of the therapy
Surgery
- Not specified
Other
- No concurrent immunosuppressive medication
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