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)

September 11, 2023 updated by: Memorial Sloan Kettering Cancer Center

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

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • After completion of study therapy, patients are followed for up to 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Assessed for Safety and Tolerability as Assessed by NCI CTCAE v3.0
Time Frame: 2 years
Participant toxicity will be evaluated by using NCI CTCAE v3.0
2 years
Total Number of Dose Limiting Toxicities/DLT's
Time Frame: 2 years
2 years
Mean Overall Survival
Time Frame: Up to 3 years
Up to 3 years
Best Response
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2007

Primary Completion (Actual)

August 3, 2021

Study Completion (Actual)

August 3, 2021

Study Registration Dates

First Submitted

November 21, 2007

First Submitted That Met QC Criteria

November 21, 2007

First Posted (Estimated)

November 22, 2007

Study Record Updates

Last Update Posted (Actual)

September 15, 2023

Last Update Submitted That Met QC Criteria

September 11, 2023

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-155
  • MSKCC-06155

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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