Allogeneic Peripheral Stem Cell Transplantation After Antithymocyte Globulin, High-Dose Melphalan, and Fludarabine in Treating
Women With Metastatic Adenocarcinoma of the Breast
This study is currently recruiting patients.
Sponsored by: |
UCSD Cancer Center
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Information provided by: |
National Cancer Institute (NCI) |
Purpose
RATIONALE: Donor peripheral stem cell transplantation may be an effective treatment for breast cancer that has not responded
to previous chemotherapy or has spread to the bone marrow. Combining antithymocyte globulin with melphalan and fludarabine
before transplantation may reduce the chance of developing graft-versus-host disease.
PURPOSE: Phase II pilot study of allogeneic peripheral stem cell transplantation after antithymocyte globulin, high-dose melphalan,
and fludarabine in treating women who have metastatic adenocarcinoma of the breast.
Condition
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Treatment or Intervention |
Phase |
recurrent breast cancer stage IV breast cancer
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Drug: allogeneic lymphocytes Drug: anti-thymocyte globulin Drug: cyclosporine Drug: filgrastim Drug: fludarabine Drug: melphalan Drug: methotrexate Procedure: biological response modifier therapy Procedure: bone marrow ablation with stem cell support Procedure: chemotherapy Procedure: colony-stimulating factor therapy Procedure: cytokine therapy Procedure: graft versus host disease prophylaxis/therapy Procedure: graft versus tumor induction Procedure: high-dose chemotherapy Procedure: leukocyte therapy Procedure: non-specific immune-modulator therapy Procedure: peripheral blood lymphocyte therapy Procedure: peripheral blood stem cell transplantation Procedure: supportive care/therapy
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Phase II
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MedlinePlus related topics: Breast Cancer
Genetics Home Reference related topics: breast cancer
Study Type: Interventional
Study Design: Treatment
Official Title: Phase II Pilot Study 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
Further Study Details:
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.
Eligibility
Ages Eligible for Study:
18 Years
-
60 Years,
Genders Eligible for Study:
Both
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
Sex
Menopausal status
Performance status
- Karnofsky 70-100% OR
- ECOG 0-1
Life expectancy
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
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
Other
- No concurrent immunosuppressive medication
Location
and Contact
Information
California Rebecca and John Moores UCSD Cancer Center, La Jolla,
California,
92093-0690,
United States; Recruiting
Asad Bashey, MD, PhD
858-657-6790
Study chairs or principal investigators
Asad Bashey, MD, PhD, Principal Investigator, UCSD Cancer Center
More Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Study ID Numbers:
CDR0000343758; UCSD-020815
Record last reviewed:
November 2003
Record first received:
December 10, 2003
ClinicalTrials.gov Identifier:
NCT00074269Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05