Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer
Condition: Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Inflammatory Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms; Breast Neoplasms, Male; Inflammatory Breast Neoplasms
Intervention: tamoxifen citrate; busulfan; thiotepa; melphalan; aldesleukin; sargramostim; peripheral blood stem cell transplantation; radiation therapy
Intervention description: Given orally; Given orally; Given IV; Given IV; Given SC; Given SC; Undergo autologous peripheral blood stem cell infusion; May undergo radiotherapy after completion of IL-2/GM-CSF
Intervention MeSH terms: Tamoxifen; Aldesleukin; Melphalan; Busulfan; Thiotepa; Interleukin-2; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 19 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving combination chemotherapy and peripheral blood
      stem cell transplant followed by aldesleukin and sargramostim works in treating patients with
      inflammatory stage IIIB or metastatic stage IV breast cancer. Drugs used in chemotherapy,
      such as busulfan, melphalan, and thiotepa, work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell
      transplant may be able to replace blood-forming cells that were destroyed by chemotherapy.
      This may allow more chemotherapy to be given so that more tumor cells are killed. Aldesleukin
      may stimulate the white blood cells to kill breast cancer cells. Giving aldesleukin together
      with sargramostim may kill more tumor cells
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with inflammatory (stage IIIb) or responsive stage IV breast cancer with
             metastasis to soft tissue and/or bone; responsive stage IV disease is defined as
             patients who achieve a PR (>= 50% reduction in measurable tumor burden) or CR
             following initial chemotherapy for metastatic disease or patients with locally
             recurrent disease (chest wall/axillary nodes) who are rendered disease-free following
             surgery or radiation therapy without receiving chemotherapy; bone disease is
             categorized as responsive if there is demonstrated sclerosis of prior lesions with no
             new lesions

          -  Patients should have received 4-7 cycles of an Adriamycin and/or taxane-based regimen
             for stage IIIb or stage IV disease; locally recurrent (chest wall/axillary nodes)
             patients rendered NED by RT or surgery do not need to receive chemotherapy for stage
             IV disease prior to Cytoxan/Taxol

          -  Patient has received Cytoxan 4 gm/m^2 x 1 and Taxol 250 mg/m^2 x 1 per FHCRC protocol
             506.03; Cytoxan/Taxol must be given after all other chemotherapy is completed and
             before transplant

          -  Stem cells were collected after mobilization with Cytoxan/Taxol or after mobilization
             from an FHCRC approved cytokine protocol; if syngeneic collection, PBSC's were
             collected by using G-CSF according to FHCRC protocol 753; patient has an adequate
             number of peripheral blood stem cells stored (>= 2.5 x 10^6 CD34+ cells/kg)

          -  The patient must have the capacity to give informed consent; the patient must have
             signed an approved consent form conforming with federal and institutional guidelines

          -  Hepatic function: Bilirubin =< 2 mg%; SGOT or SGPT =< 2.5 x institutional normal

          -  Renal function: Creatinine =< 2.0 mg/dl or a creatinine clearance >= 50 mg/min

          -  Pre-Study tests have been performed as outlined in the Study Calendar

          -  Patients will begin IL-2/GM-CSF therapy if they meet the following criteria
             post-transplant:

          -  Can start therapy 30 to 100 days after transplant

          -  Karnofsky performance status > 60

          -  ANC > 1,000 cells/mm^3 and platelets > 30,000/cells/mm^3 (transfusion independent) for
             at least 5 days before starting therapy

          -  Total bilirubin =< 2.5 x upper limit of normal

          -  SGOT =< 2.5 x upper limit of normal

          -  Creatinine =< 2.0 mg/dl

        Exclusion Criteria:

          -  Patients with a Karnofsky Performance Score less than 70

          -  Patients with a left ventricular ejection fraction less than 50 % (LVEF must be
             performed in patients with symptoms of CHF, abnormal cardiac exam or history of
             Adriamycin therapy total dose > 400 mg/m^2)

          -  Patient is pregnant

          -  Patient is seropositive for the human immunodeficiency virus

          -  Patients with a history of seizures

          -  Patients with hypersensitivity to E.coli preparations

          -  Patients with active auto-immune disease

          -  Patients with clinically significant pulmonary disease, i.e., diffusion capacity
             corrected < 60% of predicted; patients with pulmonary problems should be evaluated
             with appropriate pulmonary studies and/or consult

          -  Patients with a history of CNS lesion (brain or carcinoid meningitis)

          -  Patients with significant active infection precluding transplant

          -  Patients who have had more than one prior chemotherapy regimen for stage IV disease or
             a prior transplant for any stage disease

          -  Patients who have had CD34+ selection of their PBSC products

          -  Patients will not receive IL-2/GM-CSF therapy if they:

          -  Are > 100 days from transplant

          -  Have documented disease progression after transplant

          -  Have an active infection

          -  Manifested cardiac complications during the initial transplant period, including
             arrhythmias (that required therapy), congestive heart failure, angina, myocardial
             infarct, or decreased LVEF to < 45%

          -  Currently have pericardial effusions, pleural effusions or ascites

          -  Manifested pulmonary toxicity during the initial transplant period and have a
             diffusion capacity corrected =< 60%

          -  Are on steroids

          -  Currently have a Grade 3 toxicity from BuMelTT

          -  If the patient does not wish to receive the therapy