Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: therapeutic autologous lymphocytes; Ifosfamide, carboplatin, and etoposide (ICE) regimen; Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC); Leukapheresis; peripheral blood stem cell transplantation (PBSCT)
Intervention description: Immediately after pheresis, the lymphocytes will be activated with soluble monoclonal anti-CD3 antibody (OKT3) which cross-links the CD3 receptors on T cells and activates T cells.
The time for ATC infusions will vary from patient to patient, but the infusion rate will be based on the rate calculated from the endotoxin level in the cell product. All patients will be observed for at least 1 hr after an infusion.; Ifosfamide 2,500 mg/m2 given IV daily on day -8, -7, -6, -5, -4, and -3 prior to PBSCT. Ifosfamide 2,500 mg/m2 infused IV over 1 hour (hour 0-1) on days -8 to -3 for a total dose of 15,000 mg/m2.
Mesna will be administered per BMT Standard of Care Guideline at a dose of 25% of the total Ifosfamide dose 30 minutes prior to and then 3, 6, and 9 hours after ifosfamide daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 2500 mg/m2.
Carboplatin at a dose of 250 mg/m2 will be given daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 1500 mg/m2.
VP-16 (etoposide) at a dose of 200 mg/m2 will be given IV on days -8, -7, -6, -5, -4 and -3. The total dose of VP-16 given prior to PBSCT will be 2,400 mg/m2. VP-16 will be given 200 mg/m2; Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -4, -3, and -2 (total = 6000 mg/m2).
Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -4, -3, -2 (total = 500 mg/m2) as the preparative regimen followed by PBSCT on day 0.
Carboplatin will be given at a dose of 267 mg/m2 in D5W IV over one hour daily on days -4, -3, and -2.
Mesna will be administered per BMT Standard of Care Guidelines at a dose of 25% of the total cyclophosphamide dose 30 minutes prior to and then 3, 6, and 9 hours after cyclophosphamide daily on days -4, -3, and -2 prior to PBSCT for a total of 2000mg/m2.; Peripheral blood mononuclear cells (PBMC) will be collected by leukapheresis (for generation of ATC) prior to or post G-CSF (16 ug/kg/day) priming for collecting stem cells.; Will be collected either before or after peripheral blood stem cell collection for stem cell transplant.
Intervention MeSH terms: Cyclophosphamide; Ifosfamide; Thiotepa; Carboplatin; Etoposide; Etoposide phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
      plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and
      kill more tumor cells.

      PURPOSE: This phase II trial is studying how well chemotherapy followed by peripheral stem
      cell transplantation plus biological therapy works in treating women with stage IV breast
      cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Women with histologically documented metastatic carcinoma of the breast

               -  Bilateral disease allowed

               -  Concurrent intraductal or lobular carcinoma in situ allowed

          -  Measurable or evaluable recurrent metastatic disease (stage IV) documented by
             radiograph, CT scan, nuclear medicine scan, or physical exam

               -  Biopsy of recurrent site(s) recommended but not required

               -  Nonmeasurable disease allowed if tumor or metastatic disease has been previously
                  removed or successfully treated

          -  0 to 3+ HER2 amplification, as determined by FISH

          -  No clinical evidence of active brain metastases

               -  Patients with treated brain metastases (i.e., those who have received definitive
                  radiation, chemotherapy, and/or underwent surgery) and are stable are eligible

          -  Hormone receptor status:

               -  Estrogen or progesterone receptor positive or negative

        PATIENT CHARACTERISTICS:

          -  Menopausal status not specified

          -  Karnofsky performance status 70-100% OR ECOG performance status 0-2

          -  Life expectancy at least 3 months

          -  Granulocyte count at least 1,500/mm^3

          -  Platelet count at least 50,000/mm^3

          -  Hemoglobin greater than 8 g/dL

          -  Bilirubin less than 1.5 times normal

          -  AST, ALT, and alkaline phosphatase < 5 times upper normal

          -  Creatinine less than 1.8 mg/dL

          -  Creatinine clearance at least 60 mL/min

          -  BUN less than 1.5 times normal

          -  No myocardial infarction (MI) within the past year

          -  No history of MI (> 1 year ago) with current coronary symptoms requiring medication

          -  No current history of angina/coronary symptoms requiring medication

          -  No clinical evidence of congestive heart failure requiring medical management

          -  No significant congestive heart failure

          -  No other uncontrolled or significant cardiovascular disease

          -  Ejection fraction at least 45% at rest by MUGA

          -  Systolic BP < 130 mm Hg and diastolic BP < 80 mm Hg

               -  BP must be controlled to meet the standard by anti-hypertensive medications for
                  at least 7 days prior to the first infusion

          -  PFT-FEV_1 at least 50% predicted

          -  DLCO2 at least 50% predicted

          -  FVC at least 50% predicted

          -  No other malignancy within the past 3 years

          -  No other serious medical or psychiatric illness that would preclude study
             participation

          -  HIV negative

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Prior chemotherapy regimens allowed, including prior treatment on protocol
             WSU-2006-130

          -  Prior vaccine therapy on protocol WSU-2006-130 allowed

          -  More than 4 weeks to leukapheresis since prior hormonal therapy

          -  No radiation to the axial skeleton within 4 weeks of leukapheresis

          -  No concurrent hormonal therapy for breast cancer

               -  Hormones administered for non-disease-related condition (e.g. insulin for
                  diabetes) allowed

          -  Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed