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
1 other identifier
interventional
36
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2015
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2015
CompletedFirst Submitted
Initial submission to the registry
May 12, 2015
CompletedFirst Posted
Study publicly available on registry
May 29, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedAugust 3, 2016
August 1, 2016
4.7 years
May 12, 2015
August 1, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Number of participants with Adverse Events
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.
8 weeks
Secondary Outcomes (1)
Number of participants with Clinical responses
2 years
Study Arms (1)
Anti-NY ESO-1 TCR-transduced T cells
EXPERIMENTALPatients will receive a lymphodepleting conditioning regimen followed by an infusion of anti-NY-ESO-1 TCR-transduced T cells.
Interventions
On days -7 through -6, Cyclophosphamide 60mg/kg/day IV will be infused over 60 minutes.
On days -5 through -1, Fludarabine 25mg/m2/day IV will be infused over 30 minutes.
Modified cells will be infused IV over 30 minutes.
Eligibility Criteria
You may qualify if:
- Must be pathology or cytology confirmed cancer patients with age of one year old and over；
- Must be HLA-A2 positive, and cancer tissues express NY-ESO-1；
- There is at least one measurable disease: diameter ≥20mm or spiral CT≥10mm；
- Willing to sign a durable power of attorney；
- Able to understand and sign the Informed Consent Document；
- Performance status：ECOG 0-2；
- Life expectancy：More than 3 months；
- Patients must be willing to practice birth control for four months after receiving a lymphodepleting preconditioning regimen；
- Patients with no pregnancy and lactation；
- 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；
- 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）；
- Seronegative for hepatitis B and C viruses；
- Seronegative for human immunodeficiency virus (HIV) antibody；
- 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；
- 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.
You may not qualify if:
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
- Active systemic infections；
- Coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
- Concurrent use of systemic steroids；
- History of severe immediate hypersensitivity reaction to any of the agents used in this study；
- There are obvious dysfunctions in heart , liver，kidney and other vital organs
- T cell lymphoma and leukemia patients；
- HIV positive；
- History of coronary revascularization or ischemic symptoms；
- 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；
- 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；
- Bronchial lesions (probably shifted obstructive pneumonia or intracranial hemorrhage risk)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
Shenzhen, Guangdong, 518035, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 12, 2015
First Posted
May 29, 2015
Study Start
April 1, 2015
Primary Completion
December 1, 2019
Study Completion
December 1, 2019
Last Updated
August 3, 2016
Record last verified: 2016-08