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Investigator Initiated Phase 1 Study of TBI-1301

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ClinicalTrials.gov Identifier: NCT02366546
Recruitment Status : Active, not recruiting
First Posted : February 19, 2015
Last Update Posted : October 24, 2018
Sponsor:
Collaborators:
Takara Bio Inc.
Shionogi
Fiverings Co., Ltd.
Statcom Co. Ltd.
Information provided by (Responsible Party):
Shinichi Kageyama, Mie University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: TBI-1301 Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-center, Investigator Initiated Phase 1 Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors
Actual Study Start Date : March 2015
Actual Primary Completion Date : September 2018


Arm Intervention/treatment
Experimental: Low dose TBI-1301 with pre-treatment 1
TBI-1301(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Name: NY-ESO-1-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-1301.
Other Name: Endoxan

Experimental: High dose TBI-1301 with pre-treatment 1
TBI-1301(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Name: NY-ESO-1-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-1301.
Other Name: Endoxan

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: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Name: NY-ESO-1-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-1301.
Other Name: Endoxan

Drug: Fludarabine
Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1301 in combination with cyclophosphamide.
Other Name: Fludara

Experimental: TBI-1301 with pre-treatment 1 or 2
Arm1, 2 or 3, which is considered as optimal.
Drug: TBI-1301
TBI-1301(5*10^8 or 5*10^9) is administered.
Other Name: NY-ESO-1-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-1301.
Other Name: Endoxan

Drug: Fludarabine
Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1301 in combination with cyclophosphamide.
Other Name: Fludara




Primary Outcome Measures :
  1. 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.

  2. Appearance of replication competent retrovirus by PCR [ Time Frame: 4 weeks ]
    Confirm no replication competent retrovirus observed.

  3. Appearance of clonality by LAM-PCR [ Time Frame: 4 weeks ]
    Confirm no clonality is observed.

  4. Kinetics of TBI-1301 in blood by realtime-PCR [ Time Frame: 8 weeks ]
    Evaluate persistence and expansion of transferred TBI-1301.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02366546


Locations
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Japan
Mie University Hospital
Tsu, Mie, Japan
Sponsors and Collaborators
Mie University
Takara Bio Inc.
Shionogi
Fiverings Co., Ltd.
Statcom Co. Ltd.
Investigators
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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

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Responsible Party: Shinichi Kageyama, Professor, Mie University
ClinicalTrials.gov Identifier: NCT02366546     History of Changes
Other Study ID Numbers: 1301-01
First Posted: February 19, 2015    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018

Keywords provided by Shinichi Kageyama, Mie University:
Adoptive cell transfer
Cell therapy
Immunotherapy
NY-ESO-1
Esophageal cancer
Melanoma
Head and neck cancer
Ovarian cancer
Synovial sarcoma
TCR gene therapy

Additional relevant MeSH terms:
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Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites