Modified White Blood Cells That Secrete IL-2 and Express a Protein That Targets the ESO-1tumor Protein for Metastatic Cancer

NCT01457131 | Terminated Phase 1

• 2 other identifiers: 12000612-C-0006
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- 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. Objectives: \- To test the safety and effectiveness of anti-ESO-1/IL-12 white blood cells against metastatic cancer. Eligibility: \- Individuals at least 18 years of age who have metastatic cancer that expresses ESO-1 and has not responded to standard treatments. Design:

• 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.

Conditions

Metastatic Cancer; Metastatic Melanoma; Metastatic Renal Cancer

Keywords

Metastatic Cancer; Immunotherapy; Gene Therapy; Metastatic Melanoma; Metastatic Kidney Cancer

Outcome Measures

Primary Outcomes (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.

  4 years

Secondary Outcomes (1)

• To determine the in vivo survival of cotransduced gene-engineered cells.

  4 years

Interventions

Fludarabine DRUG

50 mg/m2, IV(in the vein)on day 5 of each 25 day cycle

Cyclophosphamide DRUG

60 mg/kg/day X 2 days IV in 250 ml D5W with mesna 15 mg/kg/day X 2 days

IL-12 & Anti-NY ESO1 TCR PBL OTHER

10(7) cells to 3 X 10(10) cells

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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 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 HLA-A\*0201 positive
• Serology:
• 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.)
• 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.
• Hematology:
• Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim.
• WBC (\> 3000/mm(3)).

You may not qualify if:

• Previous treatment with IL-12.
• 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 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 60 years old
• Documented 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)

• Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914-8. doi: 10.1073/pnas.94.5.1914.

  PMID: 9050879 BACKGROUND

• Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233-9. doi: 10.1200/JCO.2008.16.5449. Epub 2008 Sep 22.

  PMID: 18809613 BACKGROUND

• Lethe B, Lucas S, Michaux L, De Smet C, Godelaine D, Serrano A, De Plaen E, Boon T. LAGE-1, a new gene with tumor specificity. Int J Cancer. 1998 Jun 10;76(6):903-8. doi: 10.1002/(sici)1097-0215(19980610)76:63.0.co;2-1.

  PMID: 9626360 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma; Kidney Neoplasms

Interventions

fludarabine; Cyclophosphamide; Interleukin-12; Adenosine Monophosphate

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Steven A Rosenberg, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 12, 2011
• First Posted: October 21, 2011
• Study Start: October 6, 2011
• Primary Completion: August 7, 2013
• Study Completion: August 7, 2013
• Last Updated: January 8, 2019

Record last verified: 2013-08-02

Locations

US (1)