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Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00128622
Recruitment Status : Completed
First Posted : August 10, 2005
Last Update Posted : November 12, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Kim Lyerly, Duke University

Brief Summary:

RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to the cancer cells. Vaccines made from a gene-modified virus and a person's white blood cells may help the body build an effective immune response to kill cancer cells. Giving denileukin diftitox together with vaccine therapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects of giving denileukin diftitox together with vaccine therapy in treating patients with metastatic cancer that expresses carcinoembryonic antigen.

Condition or disease Intervention/treatment Phase
Breast Cancer Colorectal Cancer Lung Cancer Pancreatic Cancer Unspecified Adult Solid Tumor, Protocol Specific Biological: denileukin diftitox Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine Biological: therapeutic autologous dendritic cells Phase 1

Detailed Description:



  • Determine the safety and feasibility of two different schedules of denileukin diftitox followed by active immunotherapy comprising autologous dendritic cells infected with recombinant fowlpox-CEA(6D)-TRICOM vaccine in patients with metastatic CEA-expressing malignancies.


  • Determine the immune response to this regimen in these patients.
  • Determine, preliminarily, clinical response rate and/or time to progression in patients with assessable disease treated with this regimen.

OUTLINE: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are cultured with sargramostim (GM-CSF) and interleukin-4 for the production of dendritic cells( DC). DC are mixed with recombinant fowlpox-TRICOM to produce the vaccine. Patients are assigned to 1 of 2 cohorts according to timing of study enrollment.

  • Cohort 1: Patients receive denileukin diftitox IV over at least 15 minutes once in week 0 and vaccine therapy comprising autologous DC infected with recombinant fowlpox-CEA (6D)-TRICOM vaccine intradermally and subcutaneously once in weeks 0 (beginning 4 days after the denileukin diftitox infusion), 3, 6, and 9. If < 2 of 6 patients experience dose-limiting toxicity, a second cohort of patients is enrolled.
  • Cohort 2: Patients receive denileukin diftitox as in cohort 1 once in weeks 0, 3, 6, and 9 and vaccine as in cohort 1.

In both cohorts, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for up to 15 years.

PROJECTED ACCRUAL: A total of 6-12 patients (6 per cohort) will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Regulatory T Cell Depletion With Denileukin Diftitox Followed by Active Immunotherapy With Autologous Dendritic Cells Infected With CEA-6D Expressing Fowlpox-Tricom in Patients With Advanced or Metastatic Malignancies Expressing CEA
Study Start Date : September 2005
Actual Primary Completion Date : March 2007
Actual Study Completion Date : May 2009

Arm Intervention/treatment
Experimental: Denileukin Diftitox plus vaccine
This is a single arm Phase I safety study.
Biological: denileukin diftitox
Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine
Biological: therapeutic autologous dendritic cells

Primary Outcome Measures :
  1. Safety as measured by rate of adverse events during study drug treatment [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Rate of immune response as measured by ELISPot at week 10 [ Time Frame: 3 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed malignancy

    • Metastatic disease
  • Tumor expresses carcinoembryonic antigen (CEA), as evidenced by any of the following:

    • At least 50% of tumor expresses CEA by immunohistochemistry (IHC) with ≥ a moderate intensity of staining
    • Peripheral blood CEA level > 5.0 ng/mL
    • Tumor known to be universally CEA-positive (e.g., colon or rectal cancer)
  • Measurable or evaluable disease
  • Received or refused prior therapy with a possible survival or palliative benefit AND meets the following disease-specific criteria:

    • Patients with colorectal cancer must have experienced disease progression during ≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of the following regimens:

      • Fluorouracil or capecitabine AND oxaliplatin
      • Fluorouracil or capecitabine AND irinotecan
      • Chemotherapy in combination with bevacizumab
    • Patients with breast cancer must have experienced disease progression during ≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of the following regimens:

      • Anthracycline- or taxane-based chemotherapy
      • Chemotherapy AND trastuzumab (Herceptin®) (required for patients with tumors overexpressing HER2/neu (i.e., 3+ by IHC or positive by fluorescence in situ hybridization [FISH])
    • Patients with lung cancer must have experienced disease progression during ≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of the following regimens:

      • Platinum-based (e.g., cisplatin or carboplatin) chemotherapy (for chemotherapy-naive patients only)
      • Taxane-based (e.g., docetaxel or paclitaxel) chemotherapy OR vinorelbine (for patients who received prior chemotherapy)
    • Patients with pancreatic cancer must have experienced disease progression during prior chemotherapy, including gemcitabine
    • Patients with other malignancies must have experienced disease progression after prior first-line therapy that would confer a survival or palliative benefit, if such a therapy exists

      • Patients who experienced disease progression during prior first-line palliative chemotherapy must be advised regarding second-line therapy before study enrollment
  • Previously resected brain metastases allowed provided there is no evidence of brain metastasis within the past month by MRI or CT scan
  • No requirement for further systemic chemotherapy for ≥ 3 months
  • Hormone receptor status:

    • Not specified



  • 18 and over


  • Male or female

Menopausal status

  • Not specified

Performance status

  • Karnofsky 70-100%

Life expectancy

  • More than 6 months


  • WBC ≥ 3,000/mm^3
  • Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)
  • Platelet count ≥ 100,000/mm^3


  • Bilirubin < 1.5 mg/dL (≤ 2.0 mg/dL for patients with Gilbert's syndrome)
  • SGOT and SGPT < 1.5 times upper limit of normal
  • Albumin ≥ 3.0 g/dL
  • No active acute or chronic viral hepatitis

    • Hepatitis B surface antigen negative
    • Hepatitis C negative
  • No other hepatic disease that would preclude study treatment


  • Creatinine < 1.5 mg/dL
  • No active acute or chronic urinary tract infection


  • No New York Heart Association class III-IV cardiac disease


  • HIV negative
  • No history of autoimmune disease*, including, but not limited to, the following:

    • Inflammatory bowel disease
    • Systemic lupus erythematosus
    • Ankylosing spondylitis
    • Scleroderma
    • Multiple sclerosis
  • No active cytomegalovirus (CMV) disease

    • Patients with CMV-seropositivity are eligible
  • No other active acute or chronic infection
  • No history of allergies to eggs or any component of the study vaccine, denileukin diftitox, or diphtheria toxin NOTE: *Patients with a positive anti-nuclear antibody (ANA) ≤ 1:256 with no other evidence of autoimmune disease are eligible


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 months after completion of study treatment
  • No acute or chronic skin disorder that would preclude study treatment
  • No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer
  • No psychological or medical impediment that would preclude study compliance
  • No other serious acute or chronic illness that would preclude study treatment


Biologic therapy

  • See Disease Characteristics
  • Prior vaccine, dendritic cell, or CEA-targeted immunotherapy allowed
  • At least 4 weeks since prior and no other concurrent immunotherapy
  • Concurrent palliative single-agent trastuzumab for breast cancer allowed provided patient has been on therapy for ≥ 3 months before study entry


  • See Disease Characteristics
  • At least 4 weeks since prior and no concurrent chemotherapy

Endocrine therapy

  • At least 4 weeks since prior hormonal therapy
  • At least 6 weeks since prior steroid therapy except steroids used as premedication for chemotherapy or contrast-enhanced studies
  • No concurrent steroids, including corticosteroids administered to manage toxic effects from dendritic cell or denileukin diftitox administration
  • Concurrent palliative endocrine therapy for breast cancer allowed provided patient has been on therapy for ≥ 3 months before study entry


  • At least 4 weeks since prior and no concurrent radiotherapy


  • See Disease Characteristics


  • Recovered from all prior therapy
  • At least 4 weeks since prior investigational drugs or procedures
  • At least 4 weeks since other prior therapy
  • No other concurrent immunosuppressive therapy (e.g., azathioprine or cyclosporine)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00128622

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United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
H. Kim Lyerly
National Cancer Institute (NCI)
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Study Chair: Michael A. Morse, MD Duke Cancer Institute
Schonfeld K, Mahnke K, Schallenberg S, et al.: Treatment of melanoma bearing individuals with ONTAK® depletes regulatory T cells resulting in an augmented immune response following vaccination. [Abstract] J Invest Dermatol 126 (Suppl S3): A-594, s101, 2006.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: H. Kim Lyerly, Professor, Gen & Thor Surgery, Duke University Identifier: NCT00128622    
Other Study ID Numbers: CDR0000437795
First Posted: August 10, 2005    Key Record Dates
Last Update Posted: November 12, 2012
Last Verified: November 2012
Keywords provided by H. Kim Lyerly, Duke University:
male breast cancer
recurrent breast cancer
stage IV breast cancer
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
recurrent pancreatic cancer
extensive stage small cell lung cancer
recurrent non-small cell lung cancer
recurrent small cell lung cancer
stage IV non-small cell lung cancer
unspecified adult solid tumor, protocol specific
stage IV pancreatic cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Digestive System Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Denileukin diftitox
Antineoplastic Agents