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

August 1, 2016 updated by: Shenzhen Second People's Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518035
        • Recruiting
        • Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
        • Contact:
        • Principal Investigator:
          • Mingjun Wang, M.D., Ph.D.
        • Principal Investigator:
          • Geng Tian, M.D., Ph.D.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shenzhen Second People's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Shenzhen Institute for Innovation and Translational Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2015

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 12, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 27, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 29, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201504002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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