Treated Blood Cells, Cyclophosphamide, Fludarabine Phosphate, and Aldesleukin in Treating Patients With Cancer

February 27, 2012 updated by: Cancer Research UK

A Cancer Research UK Phase I Trial of Adoptive Transfer of Autologous Tumor Antigen-Specific T Cells With Preconditioning Chemotherapy and Intravenous IL2 in Patients With Advanced CEA Positive Tumors

RATIONALE: Placing a gene into T cells may improve the body's ability to recognize cancer cells and build an immune response to fight cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop cancer cells from growing. Giving specially treated T cells together with cyclophosphamide, fludarabine phosphate, and aldesleukin may kill more tumor cells.

PURPOSE: This phase I clinical trial is studying the side effects and best dose of treated T cells when given together with cyclophosphamide, fludarabine phosphate, and aldesleukin in treating patients with cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the feasibility of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes in combination with preconditioning chemotherapy comprising cyclophosphamide and fludarabine phosphate plus aldesleukin in patients with CEA-positive tumors.
  • To assess the toxicity of this regimen in these patients.
  • To determine the dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes required to give optimal survival of these cells in the circulation (recommended phase II dose).

Secondary

  • To assess whether MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes isolated from the circulation are functional.
  • To determine the preliminary tumor response to MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.
  • To evaluate the safety of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

OUTLINE: This is a phase I, dose-escalation study of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

Patients undergo leukapheresis 7-14 days before study therapy begins. Cells are then transduced with a retrovirus vector and expanded to produce MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

Patients receive preconditioning chemotherapy comprising fludarabine phosphate IV over 15 minutes on days -5 to -1 or cyclophosphamide IV over 1 hour on days -7 to -6 and fludarabine phosphate IV over 15 minutes on days -5 to -1. They receive MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes IV over 30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours for up to 12 doses beginning on day 0, in the absence of disease progression or unacceptable toxicity. If there is evidence of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival, patients may receive additional high-dose aldesleukin.

Patients undergo blood sample collection periodically for pharmacokinetic and pharmacodynamic studies. Some patients may undergo a tumor biopsy.

After completion of study treatment, patients are followed up every 2 weeks for 6 weeks, every 4 weeks for 6 months, every 3 months for 1 year, and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Study Type

Interventional

Enrollment (Actual)

14

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 Kingdom
    • England
      • Manchester, England, United Kingdom, M20 4BX
        • Christie Hospital

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignancy

    • Metastatic or unresectable disease
    • Standard curative or palliative measures do not exist, are no longer effective, have been completed, or have been refused
  • CEA-positive tumor (either by immunohistochemistry or as demonstrated by elevated CEA > 50 μg/L)
  • No primary brain tumor or brain metastases

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Life expectancy ≥ 3 months
  • Hemoglobin ≥ 10 g/dL
  • Platelet count ≥ 100 x 10^9/L
  • Neutrophil count ≥ 2.0 x 10^9/L
  • Lymphocyte count ≥ 1.0 x 10^9/L
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT/AST ≤ 5 times ULN
  • Alkaline phosphatase ≤ 5 times ULN
  • Calculated creatinine clearance OR isotope clearance measurement ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 4 weeks prior to, during, and for 6 months after completion of study therapy (male patients must use barrier-method contraception)
  • LVEF ≥ 50% on MUGA scan (for patients receiving cyclophosphamide)
  • ECG and exercise ECG (or stress ECHO) normal (may be abnormal but not clinically significant)
  • Urine dipstick normal (may be abnormal but not clinically significant)
  • No medical high risk due to nonmalignant systemic disease including active uncontrolled infection
  • No known serologically positive hepatitis B, hepatitis C, HIV, or HTLV
  • No history of autoimmune disease
  • No inflammatory bowel disease
  • No concurrent congestive heart failure or prior history of NYHA class III-IV cardiac disease
  • No concurrent malignancies originating from other primary sites, except for adequately treated cone-biopsied carcinoma in situ of the cervix uteri or basal cell or squamous cell carcinoma of the skin
  • No other condition that, in the investigator's opinion, would make the patient an unsuitable candidate for the clinical trial

PRIOR CONCURRENT THERAPY:

  • At least 30 days since prior and no concurrent participation in another clinical trial
  • At least 4 weeks since prior and no concurrent radiotherapy (except for palliative reasons [i.e., control of bone pain])
  • At least 4 weeks since prior and no concurrent endocrine therapy, immunotherapy, or chemotherapy (6 weeks for nitrosoureas and mitomycin C)
  • No toxic manifestations of previous treatment, except for alopecia or certain grade 1 toxicities that, in the opinion of the investigator and CRUK (Cancer Research UK), would exclude the patient (e.g., grade 1 neuropathy or grade 1 fatigue)
  • No prior major thoracic and/or abdominal surgery from which the patient has not yet recovered
  • No prior bone marrow transplant or extensive radiotherapy to > 25% of bone marrow
  • No concurrent systemic steroids or other immunosuppressive therapy
  • No other concurrent anticancer therapy or investigational drugs

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
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Percentage of patients (goal is 50%) who are evaluable for MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival
Adverse event according to CTCAE version 3 criteria
Dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes that gives the highest frequency in the circulation as measured by the primary assays (recommended phase II dose)

Secondary Outcome Measures

Outcome Measure
Presence of cells with a functional chimeric immune receptor on bCEA binding assay
Partial response or complete response on CT scans at 6, 12, 24, and 52 weeks as defined by RECIST criteria
Long-term follow up for insertional mutagenesis

Collaborators and Investigators

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

Sponsor

Cancer Research UK

Investigators

  • Principal Investigator: Robert E. Hawkins, MD, The Christie NHS Foundation Trust

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

August 1, 2007

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

September 30, 2010

First Submitted That Met QC Criteria

September 30, 2010

First Posted (Estimate)

October 1, 2010

Study Record Updates

Last Update Posted (Estimate)

February 28, 2012

Last Update Submitted That Met QC Criteria

February 27, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000685060
  • CRUK-PH1/105
  • CRUK-MFEz
  • EUDRACT-2005-004085-16
  • EU-21070

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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