Trial record 1 of 1 for:    09-C-0047
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Gene Therapy Using Anti-CEA Cells to Treat Metastatic Cancer

This study has been terminated.
(Study was terminated due to poor accrual.)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00923806
First received: June 17, 2009
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

Background:

  • Carcinoembryonic antigen (CEA) is a protein present mostly in cancer cells.
  • An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. These cells are genetically modified using the anti-CEA gene and a type of virus. The modified cells (anti-CEA cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy.

Objectives:

  • To determine whether advanced cancers that that express the CEA antigen can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-CEA protein.

Eligibility:

  • Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective.
  • Patients' tumors express the CEA antigen.
  • Patients have the human leukocyte (HLA-A*0201) antigen.

Design:

  • Workup with scans, x-rays and other tests.
  • Leukapheresis to obtain cells for preparing the anti-CEA cells for later infusion.
  • 1 week of chemotherapy to prepare the immune system for receiving the anti-CEA cells.
  • Infusion of anti-CEA cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses.
  • 1-2 weeks of recovery from the effects of chemotherapy and IL-2.
  • Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.

Condition Intervention Phase
Metastatic Cancer
Biological: PG13-CEA_TCR (Anti-CEA TCR PBL)
Drug: Aldesleukin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA) Using Lymphodepleting Conditioning Followed by Infusion of Anti-CEA TCR-Gene Engineered Lymphocytes

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • clinical response of the administration of anti-CEA TCR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen and aldesleukin in patients with metastatic cancer. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]

Enrollment: 3
Study Start Date: December 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gene Therapy Treatment Biological: PG13-CEA_TCR (Anti-CEA TCR PBL)
N/A
Drug: Aldesleukin
720,000 IU/kg intravenous over 15 minutes every 8 hours for up to 5 days
Other Name: Proleukin

  Show Detailed Description

  Eligibility

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

-INCLUSION CRITERIA:

  1. Metastatic cancer that expresses carcinoembryonic antigen (CEA) as assessed by one of the following methods:

    • Immunohistochemistry of resected tissue, assessed by immunohistochemistry (IHC) in the Clinical Laboratory Improvement Amendments (CLIA) approved test in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH). Since the affinity of the antibody is weak, a result of greater than or equal to 1+ is considered positive.
    • Detection of elevated levels of circulating CEA using a standard clinical enzyme-linked immunosorbent (ELISA) assay. Results will be considered positive if CEA level is greater than 10 mcg/L.
    • Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
  2. Hepatic metastases must represent the life limiting components of the disease defined as liver disease with a very high likelihood of causing the death of a patient according to the best clinical judgment of the attending physician.
  3. Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred.
  4. Greater than or equal to 18 years of age.
  5. Willing to sign a durable power of attorney
  6. Able to understand and sign the Informed Consent Document
  7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
  8. Life expectancy of greater than three months.
  9. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
  10. Patients must be human leukocyte antigen (HLA-A*0201) positive
  11. Serology:

    1. Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
    2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
  12. Hematology:

    1. Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
    2. White blood cell (WBC) (greater than 3000/mm^3.
    3. Platelet count greater than 100,000/mm^3.
    4. Hemoglobin greater than 8.0 g/dl.
  13. Chemistry:

    1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
    2. Serum creatinine less than or equal to 1.6 mg/dl.
    3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  14. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

EXCLUSION CRITERIA:

  1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  2. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  4. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
  5. Concurrent systemic steroid therapy
  6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  7. History of coronary revascularization or ischemic symptoms
  8. Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
  9. Documented LVEF of less than or equal to 45% tested in patients with:

    1. History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
    2. Age greater than or equal to 60 years old
  10. Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with:

    1. A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
    2. Symptoms of respiratory dysfunction
  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: NCT00923806

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Rosenberg, M.D. National Cancer Institute, National Institutes of Health
  More Information

Publications:
Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00923806     History of Changes
Obsolete Identifiers: NCT00809978
Other Study ID Numbers: 090047, 09-C-0047
Study First Received: June 17, 2009
Last Updated: October 3, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Cancer
Tumor Regression
Safety
Immunotherapy

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Aldesleukin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 23, 2014