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Modified White Blood Cells That Secrete IL-2 and Express a Protein That Targets the ESO-1tumor Protein for 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: NCT01457131
Recruitment Status : Terminated
First Posted : October 21, 2011
Last Update Posted : January 8, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


- A new cancer treatment involves collecting white blood cells from an individual, modifying them to secrete IL-2 and target the ESO-1 protein expressed on some cancers, and returning them to the body. The cells may then be able to seek out the cancer cells and destroy them. Some kinds of cancer contain a protein called ESO-1, which is found on the surface of the cells. Doctors want to modify white blood cells to have an anti-ESO-1 effect, and use them to treat the cancer that has the ESO-1. In addition to adding genes that target the ESO-1 protein to the cells, the genes for IL-12 are added to the cells. IL-12 is a protein that stimulates the immune system. This type of therapy is called gene transfer.


- To test the safety and effectiveness of anti-ESO-1/IL-12 white blood cells against metastatic cancer.


- Individuals at least 18 years of age who have metastatic cancer that expresses ESO-1 and has not responded to standard treatments.


  • Participants will be screened with a medical history and physical exam. They will also have blood tests and imaging studies.
  • Participants will have leukapheresis about a month before the treatment to collect white blood cells.
  • They will have chemotherapy 5 days before the treatment to suppress the immune system, and prepare the body for the anti-ESO-1/IL-12 cells.
  • The anti-ESO-1/IL-12 cells will be given as an infusion.
  • Participants will be monitored in the hospital during their recovery from the treatment.
  • Participants will have regular followup exams every 1 to 6 months. The exams will include blood tests, imaging studies, and other studies.

Due to toxicities seen with the regimen, it was decided not to pursue the phase 2 portion of the study.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Metastatic Melanoma Metastatic Renal Cancer Drug: Fludarabine Drug: Cyclophosphamide Other: IL-12 & Anti-NY ESO1 TCR PBL Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Gene Engineered Lymphocytes Cotransduced With Genes Encoding IL-12 and Anti-NY ESO-1 TCR
Study Start Date : October 6, 2011
Actual Primary Completion Date : August 7, 2013
Actual Study Completion Date : August 7, 2013

Intervention Details:
  • Drug: Fludarabine
    50 mg/m2, IV(in the vein)on day 5 of each 25 day cycle
  • Drug: Cyclophosphamide
    60 mg/kg/day X 2 days IV in 250 ml D5W with mesna 15 mg/kg/day X 2 days
  • Other: IL-12 & Anti-NY ESO1 TCR PBL
    10(7) cells to 3 X 10(10) cells

Primary Outcome Measures :
  1. To evaluate the safety of the IL-12 and anti-NY-ESO-1 engineered PBL in patients receiving a non-myeloablative conditioning regimen, and to determine if patients with metastatic cancer will have clinical tumor regression following this regimen. [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. To determine the in vivo survival of cotransduced gene-engineered cells. [ Time Frame: 4 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    1. Metastatic cancer that expresses ESO as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with ESO. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
    2. Patients with melanoma or renal cell cancer must have previously received high dose IL-2 and have been either non-responders (progressive disease) or have recurred. Patients with other histologies, 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.
    3. Greater than or equal to 18 years of age.
    4. Willing to sign a durable power of attorney
    5. Able to understand and sign the Informed Consent Document
    6. Clinical performance status of ECOG 0 or 1.
    7. Life expectancy of greater than three months.
    8. 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.
    9. Patients must be HLA-A*0201 positive
    10. Serology:

      1. Seronegative for 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 seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
    11. Hematology:

      1. Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim.
      2. WBC (> 3000/mm(3)).
      3. Platelet count greater than 100,000/mm(3).
      4. Hemoglobin greater than 8.0 g/dl.
    12. Chemistry:

      1. Serum ALT/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.
    13. 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).
    14. Six weeks must have elapsed since any prior anti-CTLA4 antibody therapy to allow antibody levels to decline.
    15. Patients who have previously received any anti-CTLA4 antibody and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.


  1. Previous treatment with IL-12.
  2. 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.
  3. 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.
  4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  5. 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).
  6. Concurrent systemic steroid therapy.
  7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  8. History of coronary revascularization or ischemic symptoms
  9. Any patient known to have an LVEF less than or equal to 45%.
  10. 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 60 years old
  11. Documented 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

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): NCT01457131

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)

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Responsible Party: National Cancer Institute (NCI) Identifier: NCT01457131     History of Changes
Other Study ID Numbers: 120006
First Posted: October 21, 2011    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: August 2, 2013
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Metastatic Cancer
Gene Therapy
Metastatic Melanoma
Metastatic Kidney Cancer
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Kidney Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists