Investigator Initiated Phase 1 Study of TBI-1301

October 22, 2018 updated by: Shinichi Kageyama, Mie University

Multi-center, Investigator Initiated Phase 1 Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors

Following pre-treatment with cyclophosphamide and/or fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to the patients with NY-ESO-1-expressing solid tumors.

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

Following pre-treatment with cyclophosphamide alone or in combination with fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to HLA-A*02:01 or HLA-A*02:06 positive patients with solid tumors which are 1) unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc), and 2) NY-ESO-1-expressing. The primary objective is to evaluate the safety and in vivo kinetics, and the secondary is to evaluate clinical effect.

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 (Actual)

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.
9

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 Locations

  • Japan
    • Mie
      • Tsu, Mie, Japan
        • Mie University Hospital

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

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed solid tumors
  2. Solid tumor, which is unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc)
  3. HLA-A*02:01 or HLA-A*02:06 positive
  4. NY-ESO-1-expression by PCR or immunohistochemistry
  5. ECOG Performance Status, 0 or 1
  6. Age >=20 years on consent
  7. No treatment (surgery, chemotherapy, radiotherapy, etc.) and expected sufficient recovery from the treatment at the time of the lymphocytes collection for gene transfer.
  8. Life expectancy >=16 weeks after consent

  9. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria:

    • WBC >= 2,500/μL
    • Hemoglobin >= 8.0g/dL
    • Platelets >= 75,000/μL
    • T. bilirubin < 1.5 x ULN
    • AST(GOT), ALT(GPT) < 3.0 x ULN
    • Creatinine < 1.5 x ULN
  10. Ability to understand the study contents and to give a written consent at his/her free will.

Exclusion Criteria:

  1. The following serious complications are excluded from the study;

    • Unstable angina, cardiac infarction, or heart failure
    • Uncontrolled diabetes or hypertension
    • Active infection
    • Obvious interstitial pneumonia or lung fibrosis by chest X-ray
    • Active autoimmune disease requiring steroids or immunosuppressive therapy.
  2. Serious hypersensitivity
  3. Tumor cell invasion into CNS
  4. Active multiple cancer
  5. Positive for HBs antigen or HBV-DNA observed in serum
  6. Positive for HCV antibody and HCV-RNA observed in serum
  7. Positive for antibodies against HIV or HTLV-1
  8. Left Ventricular Ejection Fraction (LVEF): <= 50％
  9. Percutaneous Oxygen saturation: < 94％
  10. History of serious hypersensitivity reactions to bovine or murine derived substances.
  11. History of hypersensitivity reaction to drugs used in this study.
  12. Psychological disorder or drug dependency which may have impact on the consent.
  13. Pregnant females, lactating females (except when they cease and don't resume lactation) or female and male patients who cannot agree to practice the adequate birth control after the consent during the study
  14. Clinically significant systemic illness that in the judgment of the PI or sub-investigator would compromise the patient's ability to tolerate protocol therapy or significantly increase the risk of complications.

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: Non-Randomized
  • 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: Low dose TBI-1301 with pre-treatment 1
TBI-1301(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
Drug: Cyclophosphamide
Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.
Other Names:
  • Endoxan
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Names:
  • NY-ESO-1-specific TCR gene transduced T lymphocytes
Experimental: High dose TBI-1301 with pre-treatment 1
TBI-1301(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
Drug: Cyclophosphamide
Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.
Other Names:
  • Endoxan
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Names:
  • NY-ESO-1-specific TCR gene transduced T lymphocytes
Experimental: High dose TBI-1301 with pre-treatment 2
TBI-1301(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
Drug: Cyclophosphamide
Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.
Other Names:
  • Endoxan
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Names:
  • NY-ESO-1-specific TCR gene transduced T lymphocytes
Drug: Fludarabine
Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1301 in combination with cyclophosphamide.
Other Names:
  • Fludara
Experimental: TBI-1301 with pre-treatment 1 or 2
Arm1, 2 or 3, which is considered as optimal.
Drug: Cyclophosphamide
Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.
Other Names:
  • Endoxan
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Names:
  • NY-ESO-1-specific TCR gene transduced T lymphocytes
Drug: Fludarabine
Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1301 in combination with cyclophosphamide.
Other Names:
  • Fludara

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
Incidence and grade of adverse events (CTCAE)
Time Frame: 4 weeks
• Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
4 weeks
Appearance of replication competent retrovirus by PCR
Time Frame: 4 weeks
Confirm no replication competent retrovirus observed.
4 weeks
Appearance of clonality by LAM-PCR
Time Frame: 4 weeks
Confirm no clonality is observed.
4 weeks
Kinetics of TBI-1301 in blood by realtime-PCR
Time Frame: 8 weeks
Evaluate persistence and expansion of transferred TBI-1301.
8 weeks

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.
Mie University

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.
Fiverings Co., Ltd.
Shionogi
Takara Bio Inc.
Statcom Co. Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Hiroshi Shiku, M.D., Ph.D., Department of Immuno-Gene Therapy, Mie University, Graduate School of Medicine Mie University Hospital
  • Principal Investigator: Shinichi Kageyama, M.D., Ph.D., Department of Immuno-Gene Therapy, Mie University, Graduate School of Medicine Mie University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

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.
March 1, 2015

Primary Completion (Actual)

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.
September 1, 2018

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).
February 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.
February 18, 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.
February 19, 2015

Study Record Updates

Last Update Posted (Actual)

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.
October 24, 2018

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.
October 22, 2018

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.
October 1, 2018

More Information

Terms related to this study

Keywords

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.
  • 1301-01

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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