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

• Status: Terminated
• Trial end date: 2008-03-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Diego
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antilymphocyte Serum; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate; Melphalan; Methotrexate

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