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)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00562640
First received: November 21, 2007
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

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)


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Biological: filgrastim
Biological: therapeutic autologous lymphocytes
Drug: cyclophosphamide
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Safety and tolerability as assessed by NCI CTCAE v3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Mean tolerated dose of autologous WT1 peptide-specific T cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Quantitation of alterations in the concentration of peptide-specific T cells in the blood at defined intervals post infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: October 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: WT1-Specific T Cells
This is a phase I dose escalating trial designed to identify tolerable, clinically active doses of Wilms' tumor gene (WT1) peptide sensitized T cells when administered alone or with nonmyelosuppressive chemotherapy in patients with recurrent or persistent, evaluable WT1+ ovarian, primary peritoneal, or fallopian tube carcinomas.
Biological: filgrastim
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.
Biological: therapeutic autologous lymphocytes
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.
Drug: cyclophosphamide
Patients enrolled in dose levels II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2
Other: laboratory biomarker analysis
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 Name: After completion of study therapy, patients are followed for up to 12 weeks.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562640

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Roisin O'Cearbhaill, MB, BCh Memorial Sloan-Kettering Cancer Center
Principal Investigator: Richard J. O'Reilly, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00562640     History of Changes
Other Study ID Numbers: 06-155, MSKCC-06155
Study First Received: November 21, 2007
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
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

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 18, 2014