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

Phase I Study of Malignancies That Express NY-ESO-1 With T Cell Receptor-transduced T Cells Targeting NY-ESO-1

INTRODUCTION

  • Org Study ID: 201504002
  • Secondary ID: N/A
  • NTC ID: NCT02457650
  • Sponsor: 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.

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.


  • Overall Status
    Recruiting
  • Start Date
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of participants with Adverse Events

Primary Outcome 1 - Timeframe: 8 weeks

CONDITION

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

ELIGIBILITY


- 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)

Gender: All

Minimum Age: N/A

Maximum Age: 1 Year

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 15814723218

Email: mingjunw429@163.com

LOCATION

Facility Status Contact
Facility: Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
Shenzhen, Guangdong 518035
China
Status: Recruiting Contact:
Mingjun Wang, M.D., Ph.D.
15814723218
mingjunw429@163.com