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)

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.

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