Clinical Trials /

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

NCT02457650

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Multiple Myeloma
Recruiting Status:

Unknown status

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02457650

Trial Eligibility

Document

Title

  • Brief Title: T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies
  • Official Title: Phase I Study of Malignancies That Express NY-ESO-1 With T Cell Receptor-transduced T Cells Targeting NY-ESO-1

Clinical Trial IDs

  • ORG STUDY ID: 201504002
  • NCT ID: NCT02457650

Conditions

  • Bladder Carcinoma
  • Breast Cancer
  • Esophagus Carcinoma
  • Lung Cancer
  • Melanoma
  • Multiple Myeloma
  • Neuroblastoma
  • Ovarian Cancer
  • Synovial Sarcoma
  • Other Metastatic Solid Cancers

Interventions

DrugSynonymsArms
CyclophosphamideAnti-NY ESO-1 TCR-transduced T cells
FludarabineAnti-NY ESO-1 TCR-transduced T cells
Anti-NY ESO-1 TCR-transduced T cellsAnti-NY ESO-1 TCR-transduced T cells

Purpose

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.

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.

Trial Arms

NameTypeDescriptionInterventions
Anti-NY ESO-1 TCR-transduced T cellsExperimentalPatients will receive a lymphodepleting conditioning regimen followed by an infusion of anti-NY-ESO-1 TCR-transduced T cells.
  • Cyclophosphamide
  • Fludarabine
  • Anti-NY ESO-1 TCR-transduced T cells

Eligibility 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)
Maximum Eligible Age:N/A
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Adverse Events
Time Frame:8 weeks
Safety Issue:
Description: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

Measure:Number of participants with Clinical responses
Time Frame:2 years
Safety Issue:
Description:To determine if the treatment can result in clinical regression of malignant tumors in the patients.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Shenzhen Second People's Hospital

Last Updated

August 3, 2016