Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: anti-thymocyte globulin; filgrastim; graft-versus-tumor induction therapy; therapeutic allogeneic lymphocytes; cyclosporine; fludarabine phosphate; melphalan; methotrexate; peripheral blood stem cell transplantation
Intervention MeSH terms: Cyclosporine; Methotrexate; Fludarabine phosphate; Fludarabine; Melphalan; Cyclosporins; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage IV 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.
    

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