Autologous T Cells With or Without Cyclophosphamide and Fludarabine in Treating Patients With Recurrent or Persistent Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer (Fludarabine Treatment Closed as of 12/01/2009)
Condition: Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer
MeSH terms: Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Peritoneal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the
      bone marrow to the blood so they can be collected. Treating stem cells collected from the
      patient's blood in the laboratory may increase the number of immune cells that can mount an
      immune response against the tumor. The treated stem cells may help destroy any remaining
      tumor cells (graft-versus-tumor effect). Chemotherapy may also be given to the patient to
      prepare the bone marrow for the stem cell transplant.

      PURPOSE: This phase I trial is studying the side effects and best dose of autologous T cells
      when given with or without cyclophosphamide and fludarabine in treating patients with
      recurrent or persistent advanced ovarian epithelial cancer, primary peritoneal cavity cancer,
      or fallopian tube cancer. (fludarabine treatment closed as of 12/012009)
    

Detailed description: 
      OBJECTIVES:

        -  To assess the safety and tolerability of in vitro expanded autologous WT1 specific T
           cells, when administered alone or in combination with non-myeloablative,
           immunosuppressive conditioning, in patients with recurrent or persistent, advanced,
           WT1-positive, ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian
           tube cancer.

        -  To determine the maximum tolerated dose of autologous WT1 specific T cells in these
           patients.

        -  To quantitate alterations in the concentration of WT1 specific T cells in the blood at
           defined intervals post infusion with or without non-myeloablative, immunosuppressive
           conditioning in order to gain estimates regarding their survival and proliferation.

        -  To assess the effects of the adoptively transferred T cells on the growth and
           progression of advanced ovarian epithelial cancer, primary peritoneal cavity cancer, or
           fallopian tube cancer.

      OUTLINE: This is a dose-escalation study of WT1 peptide-specific T cells.

        -  T-cell generation and isolation: Patients undergo collection of peripheral blood stem
           cells (PBMC) from which T cells are purified, stimulated in vitro with WT1
           peptide-pulsed autologous EBV BLCL, and expanded ex vivo.

        -  Stem cell mobilization and harvest: Patients receive filgrastim (G-CSF) subcutaneously
           daily for five days. PBMC are collected by leukapheresis on the fifth day and then
           cryopreserved for subsequent reinfusion into the patient, in the event of prolonged
           cytopenia.

        -  Autologous T-cell infusion with or without conditioning chemotherapy ( fludarabine
           treatment closed as of 12/01/2009): Approximately 4-6 weeks after T-cell sensitization,
           patients receive an infusion of autologous WT1-specific T cells over 5-10 minutes on day
           0. Patients enrolled in dose levels II and III also undergo pre-infusion lymphodepletive
           conditioning comprising cyclophosphamide IV on day -2 and fludarabine phosphate IV over
           approximately 30 minutes on days -6 to -2. After a 48-hour rest period, patients receive
           autologous WT1-specific T cells. Treatment repeats every 14 days for up to 4 courses in
           the absence of disease progression or unacceptable toxicity. Patients with responsive or
           stable disease after completion of therapy, may receive additional courses of autologous
           WT1-specific T cells every 14 days.

      Blood samples are obtained at baseline and periodically during study and assayed for
      alterations in circulating levels of WT1 peptide-specific T cells, for biochemical indices of
      tumor burden, and for radiologic evidence of tumor response. Serum CA125 levels are measured
      and the number of T cells generating interferon gamma in response to autologous EBV BLCL is
      quantitated.

      After completion of study therapy, patients are followed for up to 12 weeks.
    

Intervention name(s): filgrastim; therapeutic autologous lymphocytes; cyclophosphamide; laboratory biomarker analysis
Intervention type(s): Biological; Biological; Drug; Other
Intervention description(s): Stem cell mobilization and harvest: Patients receive filgrastim (G-CSF) subcutaneously daily for five days. PBMC are collected by leukapheresis on the fifth day and then cryopreserved for subsequent reinfusion into the patient, in the event of prolonged cytopenia.; Autologous T-cell infusion with or without conditioning chemotherapy ( fludarabine treatment closed as of 12/01/2009): Approximately 4-6 weeks after T-cell sensitization, patients receive an infusion of autologous WT1-specific T cells over 5-10 minutes on day 0. Patients enrolled in dose levels II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2 and fludarabine phosphate IV over approximately 30 minutes on days -6 to -2. After a 48-hour rest period, patients receive autologous WT1-specific T cells. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after completion of therapy, may receive additional courses of autologous WT1-specific T cells every 14 days.; Patients enrolled in dose levels II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2; Obtained prior to adoptive therapy to quantitate baseline levels of WT1 reactive T cells, by quantitation of WT1 specific CTLp by LDA, T cells secreting IFNγ in response to peptide and, in HLA A0201+ patients, T cell binding WT1 peptide HLA A2 tetramers.
Other intervention name(s): After completion of study therapy, patients are followed for up to 12 weeks.
Intervention MeSH terms: Cyclophosphamide
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent primary peritoneal cavity cancer; stage IIIA primary peritoneal cavity cancer; stage IIIB primary peritoneal cavity cancer; stage IIIC primary peritoneal cavity cancer; stage IV primary peritoneal cavity cancer; recurrent fallopian tube cancer; stage IIIA fallopian tube cancer; stage IIIB fallopian tube cancer; stage IIIC fallopian tube cancer; stage IV fallopian tube cancer; stage IIIA ovarian epithelial cancer; stage IIIB ovarian epithelial cancer; stage IIIC ovarian epithelial cancer; 06-155