Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer
Condition: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Breast Cancer
MeSH terms: Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms
Intervention: Fludarabine; Cyclophosphamide; Cyclosporine; Natural killer cells; IL-2; Methylprednisolone; Methylprednisolone; Interleukin-2
Intervention description: Administered intravenously, 25 mg/m^2, days -6 through -2 (5 days).; Administered intravenously, 60 mg/kg, days -5 and -4.; Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14; Administered by infusion over less than 1 hour, no more than 8.0 x 10^7 cells/kg will be given.; Will be given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 5 million units/m^2 3 times per week for 6 doses).; Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9; Administered intravenously (IV) 1 mg/kg Days -2 to +9; Will be given subcutaneously at million units 3 times a week for a total of 3 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 3 million units/m^2 3 times per week for 6 doses).
Intervention MeSH terms: Cyclosporine; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Fludarabine; Interleukin-2; Cyclosporins; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent ovarian cancer; recurrent fallopian tube cancer; recurrent primary peritoneal cancer; refractory ovarian cancer; refractory fallopian tube cancer; refractory peritoneal cancer; metastatic breast cancer

Summary:

      This is a single center phase II trial designed to optimize a clinical platform of
      lymphodepleting chemotherapy and T-cell suppression to promote the persistence, function, and
      expansion of allogeneic natural killer (NK) cells in patients with recurrent ovarian,
      fallopian tube, primary peritoneal cancer and advanced metastatic breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of recurrent ovarian cancer, fallopian tube, or primary peritoneal cancer
             that has failed or progressed after at least 2 prior salvage chemotherapy regimens
             (directed at recurrent/metastatic disease).

        OR

          -  Diagnosis of metastatic breast cancer (female or male) that has progressed on or
             failed at least one salvage chemotherapy regimen for metastatic disease and that meets
             the following disease specific related criteria:

               -  If estrogen receptor or progesterone receptor positive must have progressed on
                  prior hormonal therapy and/or

               -  if HER2-neu positive must have progressed on trastuzumab, lapatinib, or similar
                  agent

        Women with a history of both cancers are eligible for this study provided that they
        currently meet eligibility for one of the diseases. Women who have had another malignancy
        and have been disease free for at least 3 year, or with a history of completely resected
        non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.

          -  Measurable disease per disease specific Response Evaluation Criteria in Solid Tumors
             (RECIST) version 1.1 - patients with bone as their only site of disease will not be
             eligible.

          -  If history of brain metastases must be stable for at least 3 months after treatment -
             A brain computed tomography (CT) scan will only be required in subjects with known
             brain metastases at the time of enrollment or in subjects with clinical signs or
             symptoms suggestive of brain metastases.

          -  Available related HLA-haploidentical natural killer (NK) cell donor (by at least class
             I serologic typing at the A&B locus)

          -  Age 18 years or older

          -  Karnofsky performance status > or = 50%

          -  Adequate organ function as determined by the following criteria within 14 days of
             study enrollment

               -  Bone marrow: platelets > or = 80,000 x 10^9/L and hemoglobin > or = 9 g/dL,
                  unsupported by transfusions; absolute neutrophil count (ANC) > or = 1000 x
                  10^9/L, unsupported by growth colony stimulating factor (G-CSF) or
                  granulocyte-macrophage colony-stimulating factor (GM-CSF)

          -  Renal function: creatinine (Cr) < or = 2.0 mg/dL

          -  Liver function: Aspartate aminotransferase (AST), Alanine transaminase (ALT), total
             bilirubin, alkaline phosphatase < 5 times upper limit of institutional normal (ULN)

          -  Cardiac: Left ventricular ejection fraction >40% (within 28 days of treatment start)

          -  Pulmonary function: >50% corrected Carbon Monoxide Diffusing Capacity (DLCO) and
             Forced Expiratory Volume in One Second (FEV1), if presence of pleural effusion due to
             metastatic disease >40% corrected DLCO and FEV1 is acceptable (within 28 days of
             treatment start)

          -  Able to be off prednisone or other immunosuppressive medications for at least 3 days
             prior to Day 0

          -  At least 14 days must lapse between last prior anti-cancer treatment and 1st day of
             preparative regimen

          -  Voluntary written informed consent

        Exclusion Criteria:

          -  Pregnant or nursing - The agents used in this study may be teratogenic to a fetus and
             there is no information on the excretion of agents into breast milk. Participants of
             childbearing potential must have a blood test or urine study within 14 days prior to
             registration to rule out pregnancy and agree to use adequate birth control during
             study treatment

          -  Active infection - subjects must be afebrile, off antibiotics, and with no
             uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or
             biopsies) are allowed