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Investigator Initiated Phase 1 Study of TBI-1201

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02096614
Recruitment Status : Unknown
Verified November 2017 by Shinichi Kageyama, Mie University.
Recruitment status was:  Recruiting
First Posted : March 26, 2014
Last Update Posted : November 8, 2017
Sponsor:
Collaborators:
Takara Bio Inc.
Shionogi
Fiverings Co., Ltd.
Statcom Co. Ltd.
Information provided by (Responsible Party):
Shinichi Kageyama, Mie University

Tracking Information
First Submitted Date  ICMJE March 19, 2014
First Posted Date  ICMJE March 26, 2014
Last Update Posted Date November 8, 2017
Study Start Date  ICMJE April 2014
Estimated Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
  • Incidence and grade of adverse events (CTCAE) [ Time Frame: 8 weeks ]
    Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
  • Appearance of replication competent retrovirus by PCR [ Time Frame: 8 weeks ]
    Confirm no replication competent retrovirus observed
  • Appearance of clonality by LAM-PCR [ Time Frame: 8 weeks ]
    Confirm no clonality is observed
  • Kinetics of TBI-1201 in blood by realtime-PCR and flow cytometry [ Time Frame: 8 weeks ]
    Evaluate persistence and expansion of transferred TBI-1201
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2014)
  • Toxicity Profile [ Time Frame: 8 weeks ]
    Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
  • Appearance of replication competent retrovirus [ Time Frame: 8 weeks ]
    Confirm no replication competent retrovirus observed
  • Appearance of clonality [ Time Frame: 8 weeks ]
    Confirm no clonality is observed
  • Kinetics of TBI-1201 in blood [ Time Frame: 8 weeks ]
    Evaluate persistence and expansion of transferred TBI-1201
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigator Initiated Phase 1 Study of TBI-1201
Official Title  ICMJE Multi-center, Investigator Initiated Phase 1 Study of MAGE-A4 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors
Brief Summary Following pre-treatment with cyclophosphamide and/or fludarabine, MAGE-A4-specific TCR gene transduced T lymphocytes are transferred to the patients with MAGE-A4-expressing solid tumors.
Detailed Description Following pre-treatment with cyclophosphamide alone or in combination with fludarabine, MAGE-A4-specific TCR gene transduced T lymphocytes are transferred to HLA-A*24:02 positive patients with solid tumors which are 1) unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc), metastatic or recurrent, and 2) MAGE-A4-expressing. The primary objective is to evaluate the safety and in vivo kinetics, and the secondary is to evaluate clinical effect.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE
  • Drug: TBI-1201
    TBI-1201(5*10^8 or 5*10^9) is administered.
    Other Name: MAGE-A4-specific TCR gene transduced T lymphocytes
  • Drug: Cyclophosphamide
    Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201
    Other Name: Endoxan
  • Drug: Fludarabine
    Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1201 in combination with cyclophosphamide.
    Other Name: Fludara
Study Arms  ICMJE
  • Experimental: Low dose TBI-1201 with pre-treatment 1
    TBI-1201(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
    Interventions:
    • Drug: TBI-1201
    • Drug: Cyclophosphamide
  • Experimental: High dose TBI-1201 with pre-treatment 1
    TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
    Interventions:
    • Drug: TBI-1201
    • Drug: Cyclophosphamide
  • Experimental: High dose TBI-1201 with pre-treatment 2
    TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
    Interventions:
    • Drug: TBI-1201
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
  • Experimental: TBI-1201 with pre-treatment 1 or 2
    Arm1, 2 or 3, which is considered as optimal.
    Interventions:
    • Drug: TBI-1201
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 23, 2014)
12
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically or cytologically confirmed solid tumors
  2. Solid tumor, which is unresectable , refractory to standard therapy (chemotherapy, radiotherapy, etc) , metastatic or recurrent
  3. HLA-A*24:02 positive
  4. MAGE-A4-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/antibody, HBc antibody, or HCV antibody, and virus DNA observed in serum, except for HBs antibody positive case who had vaccine injection before.
  6. Positive for antibodies against HIV or HTLV-1
  7. Left Ventricular Ejection Fraction (LVEF): =< 50%
  8. Percutaneous Oxygen saturation: < 94%
  9. History of hypersensitivity reactions to bovine or murine derived substances.
  10. History of hypersensitivity reaction to drugs used in this study
  11. Psychological disorder or drug dependency which may have impact on the consent.
  12. 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
  13. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02096614
Other Study ID Numbers  ICMJE 1201-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shinichi Kageyama, Mie University
Study Sponsor  ICMJE Mie University
Collaborators  ICMJE
  • Takara Bio Inc.
  • Shionogi
  • Fiverings Co., Ltd.
  • Statcom Co. Ltd.
Investigators  ICMJE
Study Chair: Hiroshi Shiku, M.D., Ph.D. Department of Immuno-Gene Therapy, Mie University, graduate School of Medicine
Principal Investigator: Shinichi Kageyama, M.D., Ph.D. Mie University Hospital
PRS Account Mie University
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP