Gene Therapy Using Anti-CEA Cells to Treat Metastatic Cancer

NCT00923806 | Terminated Phase 1 DMC

• 2 other identifiers: 09004709-C-0047
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Cancer

Keywords

Metastatic Cancer; Tumor Regression; Safety; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (1)

• Safety

Study Arms (1)

Gene Therapy Treatment

EXPERIMENTAL

Biological: PG13-CEA_TCR (Anti-CEA TCR PBL); Drug: Aldesleukin

Interventions

PG13-CEA_TCR (Anti-CEA TCR PBL) BIOLOGICAL

Gene Therapy Treatment

Aldesleukin DRUG

720,000 IU/kg intravenous over 15 minutes every 8 hours for up to 5 days

Also known as: Proleukin

Gene Therapy Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• Greater than or equal to 18 years of age.
• Willing to sign a durable power of attorney
• Able to understand and sign the Informed Consent Document
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Life expectancy of greater than three months.
• 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.
• Patients must be human leukocyte antigen (HLA-A\*0201) positive
• Serology:
• 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.)

You may not qualify if:

• 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.
• 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.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• 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).
• Concurrent systemic steroid therapy
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
• Documented LVEF of less than or equal to 45% tested in patients with:
• 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
• Age greater than or equal to 60 years old
• Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with:
• A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
• Symptoms of respiratory dysfunction

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. doi: 10.1126/science.1076514. Epub 2002 Sep 19.

  PMID: 12242449 BACKGROUND

• Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol. 2006 May;6(5):383-93. doi: 10.1038/nri1842.

  PMID: 16622476 BACKGROUND

• Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346-57. doi: 10.1200/JCO.2005.00.240.

  PMID: 15800326 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Steven Rosenberg, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: December 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)