Breast Cancer Clinical Trial

Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer

Summary

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.

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Full Description

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.

View Eligibility Criteria

Eligibility Criteria

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

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

5

Study ID:

NCT00074269

Recruitment Status:

Terminated

Sponsor:

University of California, San Diego

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There is 1 Location for this study

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Rebecca and John Moores UCSD Cancer Center
La Jolla California, 92093, United States

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

5

Study ID:

NCT00074269

Recruitment Status:

Terminated

Sponsor:


University of California, San Diego

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