Allogeneic Natural Killer (NK) Cells in Patients With Advanced Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fludarabine; Cyclophosphamide; Total body irradiation; Natural killer cell infusion; Interleukin-2
Intervention description: administered intravenously 25 mg/m^2 times 5 doses; administered intravenously 60 mg/kg days times 2 doses.; 200 cGy (gray) on day -1; Infused cell dose is within the range of 1.5-8.0 x 10^7/kg. Cell counts are based on total cells infused after the activation culture and washing determined on the morning of infusion.; administered subcutaneously (10 MU) 3 times per week for 6 doses
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; male breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Giving chemotherapy before a donor natural killer (NK) cell infusion helps stop
      the growth of tumor cells. It also helps stop the patient's immune system from rejecting the
      donor's cells. Giving NK cells from a related donor may kill the tumor cells.

      PURPOSE: This study furthers the research of previous studies (MT2003-01 and MT2004-25) which
      were to determine a specific preparatory regimen (cyclophosphamide and fludarabine) could
      create an environment in which infused NK cells can grow and effectively treat patients with
      relapsed AML. This study will test the previous regimen in patients with breast cancer.
    

Eligibility criteria:

        Inclusion criteria:

          -  Diagnosis of metastatic breast cancer that has progressed on or failed at least one
             salvage chemotherapy regimen for metastatic disease and that meets the following
             disease specific related criteria:

               -  Measureable metastatic disease per Response Evaluation Criteria In Solid Tumor
                  (RECIST) - bone only not eligible.

               -  Disease progression while receiving prior therapy with a hormonal agent (if
                  estrogen/progesterone receptor-positive) and/or trastuzumab (Herceptin®) (if
                  HER2-neu positive)

               -  Brain metastases allowed provided they are stable for ≥ 3 months after prior
                  treatment

          -  Related HLA-haploidentical natural killer cell donor available (by ≥ class I serologic
             typing)

          -  Male or female

          -  Performance status 50-100%

          -  Platelet count ≥ 80,000/mm³ (unsupported by transfusions)

          -  Hemoglobin ≥ 9 g/dL (unsupported by transfusions)

          -  Absolute neutrophil count ≥ 1,000/mm³ (unsupported by sargramostim [GM-CSF] or
             filgrastim [G-CSF])

          -  Creatinine ≤ 2.0 mg/dL

          -  Liver function tests < 5 times normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  LVEF > 40%*

          -  Pulmonary function > 50%* (DLCO corrected AND FEV_1)

          -  No active infection (i.e., afebrile, off antibiotics, and no uninvestigated radiologic
             lesions)

        Exclusion Criteria:

          -  At least 3 days since prior prednisone or other immunosuppressive medications

          -  No other concurrent therapy for cancer