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Trial record 41 of 100 for:    "Sarcoma, Synovial"

T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies

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ClinicalTrials.gov Identifier: NCT02457650
Recruitment Status : Recruiting
First Posted : May 29, 2015
Last Update Posted : August 3, 2016
Sponsor:
Collaborator:
Shenzhen Institute for Innovation and Translational Medicine
Information provided by (Responsible Party):
Shenzhen Second People's Hospital

Brief Summary:

Background:

Autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies. The patients pretreated with a lymphodepleting preconditioning regimen will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.

Objectives:

To evaluate the safety and the efficacy of anti-NY-ESO-1 TCR-transduced T cell-based immunotherapy for patients with NY-ESO-1- expressing malignancies.

Eligibility:

Patients older than one year of age, who have relapsed or refractory malignancies that express both NY-ESO-1 and human leukocyte antigen (HLA)-A2 molecules.

Patients must have adequate organ functions.

Design:

  • Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding an HLA-A2 restricted anti-NY-ESO-1 TCR gene.
  • Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
  • Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
  • Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.

Condition or disease Intervention/treatment Phase
Bladder Carcinoma Breast Cancer Esophagus Carcinoma Lung Cancer Melanoma Multiple Myeloma Neuroblastoma Ovarian Cancer Synovial Sarcoma Other Metastatic Solid Cancers Drug: Cyclophosphamide Drug: Fludarabine Biological: Anti-NY ESO-1 TCR-transduced T cells Phase 1

Detailed Description:

Despite advances has been made to date in the treatment of patients with hematologic malignancies, clinical trials targeting solid cancers have achieved limited efficacy. One important reason is due to lack of ideal cancer antigens. NY-ESO-1 is expressed in various types of cancers, including neuroblastoma, hepatoma, myeloma, melanoma, esophagus, prostate, bladder, breast and ovarian cancers. While, in normal somatic tissues, NY-ESO-1 expression is restricted to the germline cells, which lack HLA molecules and cannot present peptides derived from NY-ESO-1 for recognition by T cells. Therefore, NY-ESO-1 specific T cells will only recognize and kill NY-ESO-1-expressing cancer cells, but not normal cells, thus avoiding induction of autoimmune reaction. With these unique features, NY-ESO-1 has been selected as an attractive tumor antigen candidate for cancer immunotherapy in various clinical trials.

In this trial, autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies after they receive a lymphodepleting preconditioning regimen. The patients will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.

Primary objectives:

To determine the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.

Secondary objectives:

To determine if the treatment can result in clinical regression of malignant tumors in the patients.

To determine the in vivo persistency of the anti-NY-ESO-1 TCR-transduced T cells.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Malignancies That Express NY-ESO-1 With T Cell Receptor-transduced T Cells Targeting NY-ESO-1
Study Start Date : April 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Anti-NY ESO-1 TCR-transduced T cells
Patients will receive a lymphodepleting conditioning regimen followed by an infusion of anti-NY-ESO-1 TCR-transduced T cells.
Drug: Cyclophosphamide
On days -7 through -6, Cyclophosphamide 60mg/kg/day IV will be infused over 60 minutes.

Drug: Fludarabine
On days -5 through -1, Fludarabine 25mg/m2/day IV will be infused over 30 minutes.

Biological: Anti-NY ESO-1 TCR-transduced T cells
Modified cells will be infused IV over 30 minutes.




Primary Outcome Measures :
  1. Number of participants with Adverse Events [ Time Frame: 8 weeks ]
    To evaluate the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.


Secondary Outcome Measures :
  1. Number of participants with Clinical responses [ Time Frame: 2 years ]
    To determine if the treatment can result in clinical regression of malignant tumors in the patients.



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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria:

    1. Must be pathology or cytology confirmed cancer patients with age of one year old and over;
    2. Must be HLA-A2 positive, and cancer tissues express NY-ESO-1;
    3. There is at least one measurable disease: diameter ≥20mm or spiral CT≥10mm;
    4. Willing to sign a durable power of attorney;
    5. Able to understand and sign the Informed Consent Document;
    6. Performance status:ECOG 0-2;
    7. Life expectancy:More than 3 months;
    8. Patients must be willing to practice birth control for four months after receiving a lymphodepleting preconditioning regimen;
    9. Patients with no pregnancy and lactation;
    10. Hematopoietic: (1) Absolute neutrophil count > 1000/mm3 without support of filgrastim; (2) Platelet count > 100,000/mm3; (3) Hemoglobin > 8.0 g/dL; (4) lymphocyte count >500/mm3; (5) WBC > 3,000/mm3;
    11. Chemistry: (1) AST and ALT < 2.5 times upper limit of normal; (2) Serum creatinine≤1.6 mg/dl; (3) Bilirubin ≤1.5 mg/dL(3.0 mg/dL in patients with Gilbert's syndrome);
    12. Seronegative for hepatitis B and C viruses;
    13. Seronegative for human immunodeficiency virus (HIV) antibody;
    14. More than four weeks must have elapsed since any prior systemic therapy at the time of randomization, and patients' toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria;
    15. Six weeks must have elapsed since any prior anti-CTLA4 antibody therapy to allow antibody levels to decline. Patients who have previously received any anti-CTLA4 antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.
  • Exclusion Criteria:

    1. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease);
    2. Active systemic infections;
    3. Coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system;
    4. Concurrent use of systemic steroids;
    5. History of severe immediate hypersensitivity reaction to any of the agents used in this study;
    6. There are obvious dysfunctions in heart , liver,kidney and other vital organs
    7. T cell lymphoma and leukemia patients;
    8. HIV positive;
    9. History of coronary revascularization or ischemic symptoms;
    10. Documented Left Ventricular Ejection Fraction (LVEF) of less than or equal to 45 percent tested in patients with: Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block;
    11. Documented forced expiratory volume 1 (FEV1) less than or equal to 60 percent predicted tested in patients with a prolonged history of cigarette smoking (20 pk/yrs of smoking) or symptoms of respiratory dysfunction;
    12. Bronchial lesions (probably shifted obstructive pneumonia or intracranial hemorrhage risk)

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 ClinicalTrials.gov identifier (NCT number): NCT02457650


Contacts
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Contact: Mingjun Wang, M.D., Ph.D. 15814723218 mingjunw429@163.com
Contact: Geng Tian, M.D., Ph.D 13724395569 tiangeng666@aliyun.com

Locations
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China, Guangdong
Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Recruiting
Shenzhen, Guangdong, China, 518035
Contact: Mingjun Wang, M.D., Ph.D.    15814723218    mingjunw429@163.com   
Contact: Geng Tian, M.D., Ph.D.    13724395569    tiangeng666@aliyun.com   
Principal Investigator: Geng Tian, M.D., Ph.D.         
Principal Investigator: Mingjun Wang, M.D., Ph.D.         
Sponsors and Collaborators
Shenzhen Second People's Hospital
Shenzhen Institute for Innovation and Translational Medicine

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Responsible Party: Shenzhen Second People's Hospital
ClinicalTrials.gov Identifier: NCT02457650     History of Changes
Other Study ID Numbers: 201504002
First Posted: May 29, 2015    Key Record Dates
Last Update Posted: August 3, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
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Sarcoma, Synovial
Carcinoma
Multiple Myeloma
Neuroblastoma
Urinary Bladder Neoplasms
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Urologic Neoplasms