A Phase I Dose Escalation Safety and Feasibility Study of WT1-Specific T Cells for the Treatment of Patients With Advanced Ovarian, Primary Peritoneal, and Fallopian Tube Carcinomas
- 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
- To determine the maximum tolerated dose of autologous WT1 specific T cells in these
- 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
- 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability as assessed by NCI CTCAE v3.0
Roisin O'Cearbhaill, MB, BCh
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|