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
Intervention: filgrastim; therapeutic autologous lymphocytes; cyclophosphamide; laboratory biomarker analysis
Intervention description: 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.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
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

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)
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Pathologically confirmed ovarian epithelial carcinoma, primary peritoneal cavity
             carcinoma, or fallopian tube carcinoma

               -  Recurrent or persistent disease after treatment with platinum-based chemotherapy

                    -  Must have platinum-resistant or intolerant disease

          -  Evaluable disease, as demonstrated by serological (i.e., CA 125), radiological, or
             pathological studies

          -  Tumor must express the Wilms Tumor Gene 1 (WT1) peptide, as detected by IHC analysis
             of banked (i.e., paraffin-embedded) or freshly biopsied tumor nodules

               -  Only WT1 tumors graded as moderate to strong (scores 4-12) according to adapted
                  German Immunoreactive Score criteria are considered positive

          -  No prior or concurrent brain metastases

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status (PS) 70-100% OR WHO PS 0-1

          -  Life expectancy ≥ 6 months

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60mL/min

          -  ALT and AST ≤ 2.5 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 times ULN

          -  Adequate pulmonary and cardiac function

          -  No clinical evidence of cardiopulmonary disease, which, in the opinion of the
             investigator, would preclude enrollment

          -  Able to keep scheduled visits

          -  No known hepatitis B or C infection

          -  No known HIV positivity

          -  No evidence of bowel obstruction

          -  No clinically significant heart disease (New York Heart Association class III or IV)

          -  No active infections requiring antibiotics within two weeks of study entry

          -  No serious intercurrent illness requiring hospitalization

          -  No history of primary or secondary immunodeficiency or autoimmune disease

          -  No other cancers except nonmelanomatous skin cancer within the past 5 years

          -  Not pregnant or lactating

          -  No other issue which, in the opinion of the treating physician, would make the patient
             ineligible for the study

        PRIOR CONCURRENT THERAPY:

          -  More than 3 weeks since prior anticancer therapy (i.e., chemotherapy, biologic
             therapy, or immunotherapy)

          -  No history of whole abdominal radiation therapy