Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer
Condition: Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: Allopurinol; Cyclophosphamide; Fludarabine phosphate; total-body irradiation; Allogeneic natural killer cells; Aldesleukin
Intervention description: All patients are to receive allopurinol 300 mg PO daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post natural killer cell infusion.; 60 mg/m^2 on Days 4 and 5 preceding natural killer cell infusion.; 25 mg/m^2 on Days 6 through 2 preceding natural killer cell infusion.; 200 cGy Day 1 preceding natural killer cell infusion.; Given day 0 - dose of 1.5-8.0 * 10^7/kg; 10 MU 3 times/week for a total of 6 doses beginning Day 0
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Allopurinol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent ovarian epithelial cancer; recurrent ovarian germ cell tumor; stage IV ovarian epithelial cancer; stage IV ovarian germ cell tumor; fallopian tube cancer; peritoneal cavity cancer

Summary:

      RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, and total-body
      irradiation before a donor natural killer cell infusion helps stop the growth of tumor cells.
      It also helps stop the patient's immune system from rejecting the donor's natural killer
      cells. Aldesleukin may stimulate the natural killer cells to kill ovarian, fallopian tube, or
      primary peritoneal cancer cells. Treating the donor natural killer cells with aldesleukin may
      help the natural killer cells kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving laboratory-treated donor natural
      killer cells together with aldesleukin works when given after cyclophosphamide, fludarabine,
      and total-body irradiation in treating patients with recurrent and/or metastatic ovarian,
      fallopian tube, or primary peritoneal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of recurrent ovarian cancer, fallopian tube, or primary peritoneal cancer
             who meets the following criteria:

          -  Measurable disease (≥ 1 cm) per Response Evaluation Criteria for Solid Tumors (RECIST)
             - patients with bone as their only site of metastatic disease will not be eligible

          -  Progression on or failure to respond to at least 2 salvage chemotherapy regimens (2
             regimens given for disease recurrence) for recurrent/metastatic ovarian, fallopian
             tube, or primary peritoneal cancer

          -  If history of brain metastases, 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 new clinical signs or
             symptoms suggestive of brain metastases.

          -  Available related HLA-haploidentical natural killer (NK) cell donor (by at least class
             I serologic typing). If biologic parents or siblings are available, can proceed with
             work-up of subject prior to return of human leukocyte antigen (HLA) typing results.

          -  Age 18 years or older

          -  Gynecology Oncology Group (GOG) performance status 0 or 1

          -  Adequate organ function as determined by the following criteria within 14 days of
             study enrollment:

               -  Bone marrow: platelets ≥ 80,000 x 10^9/L and hemoglobin ≥ 9g/dL, unsupported by
                  transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10^9/L, unsupported by
                  granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony
                  stimulating factor (GM-CSF)

               -  Renal function: creatinine (Cr) ≤ 2.0 mg/dL

               -  Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT),
                  total bilirubin, alkaline phosphatase < 5 times upper limit of institutional
                  normal

               -  Cardiac: Left ventricular ejection fraction >40%

               -  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 acceptable.

          -  Able to be off prednisone or other immunosuppressive medications for at least 3 days
             prior to Day 0

          -  Voluntary written informed consent signed before performance of any study related
             procedure not part of normal medical care.

        Exclusion Criteria:

          -  Pregnant or lactating - 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. All females
             of childbearing potential must have a blood test or urine study within 14 days prior
             to registration to rule out pregnancy.

          -  Active infection - subjects must be afebrile, off antibiotics, and with no
             uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or
             biopsies are allowed).

        Human anti-mouse antibody (HAMA) monitoring: All subjects will be questioned about prior
        exposure to antibody therapy (including OKT3, Rituximab, Trastuzumab, etc). Responses will
        be recorded and reported to the FDA as part of the annual report. For subjects with no
        prior antibody therapy exposure, no further action will be taken. For subjects who have
        received previous antibody therapies 10 ml of serum (red top tube) will be drawn before
        starting therapy and banked per section 8.1. The presence of HAMA will not exclude a
        patient from the study.