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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

Phase 1
18 Years
Open (Enrolling by invite only)
Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

Thank you

Trial Information

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
tube cancer.

- 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.

Inclusion Criteria


- 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


- 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


- More than 3 weeks since prior anticancer therapy (i.e., chemotherapy, biologic
therapy, or immunotherapy)

- No history of whole abdominal radiation therapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability as assessed by NCI CTCAE v3.0

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Roisin O'Cearbhaill, MB, BCh

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2007

Completion Date:

December 2013

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • 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
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021