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

This study has been terminated.
(due to safety concerns and lack of efficacy)
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK
ClinicalTrials.gov Identifier:
NCT01212887
First received: September 30, 2010
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Colorectal Cancer
Gastric Cancer
Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Biological: MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes
Biological: aldesleukin
Drug: cyclophosphamide
Drug: fludarabine phosphate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Cancer Research UK:

Primary Outcome Measures:
  • Percentage of patients (goal is 50%) who are evaluable for MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival [ Designated as safety issue: No ]
  • Adverse event according to CTCAE version 3 criteria [ Designated as safety issue: Yes ]
  • 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) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Presence of cells with a functional chimeric immune receptor on bCEA binding assay [ Designated as safety issue: No ]
  • Partial response or complete response on CT scans at 6, 12, 24, and 52 weeks as defined by RECIST criteria [ Designated as safety issue: No ]
  • Long-term follow up for insertional mutagenesis [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: August 2007
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01212887

Locations
United Kingdom
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Robert E. Hawkins, MD Christie Hospital NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT01212887     History of Changes
Other Study ID Numbers: CDR0000685060, CRUK-PH1/105, CRUK-MFEz, EUDRACT-2005-004085-16, EU-21070
Study First Received: September 30, 2010
Last Updated: February 27, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cancer Research UK:
unspecified adult solid tumor, protocol specific
recurrent colon cancer
stage IIIA colon cancer
stage IIIB colon cancer
stage IIIC colon cancer
stage IV colon cancer
stage IVB colon cancer
recurrent rectal cancer
stage IIIA rectal cancer
stage IIIB rectal cancer
stage IIIC rectal cancer
stage IVA rectal cancer
stage IVB rectal cancer
recurrent gastric cancer
stage IV gastric cancer
recurrent pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
recurrent breast cancer
stage IIIC breast cancer
stage IV breast cancer
extensive stage small cell lung cancer
recurrent non-small cell lung cancer
recurrent small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage IIIA ovarian epithelial cancer

Additional relevant MeSH terms:
Breast Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Adnexal Diseases
Breast Diseases
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Intestinal Diseases
Intestinal Neoplasms
Lung Diseases
Neoplasms
Neoplasms by Site
Ovarian Diseases
Pancreatic Diseases
Rectal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Skin Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on November 23, 2014