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Investigator Initiated Phase 1 Study of TBI-1201

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ClinicalTrials.gov Identifier: NCT02096614
Recruitment Status : Completed
First Posted : March 26, 2014
Last Update Posted : June 18, 2021
Sponsor:
Collaborators:
Takara Bio Inc.
Shionogi
Fiverings Co., Ltd.
Statcom Co. Ltd.
Information provided by (Responsible Party):
Shinichi Kageyama, Mie University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: TBI-1201 Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 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 MAGE-A4 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors
Study Start Date : April 2014
Actual Primary Completion Date : March 2021
Actual Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Low dose TBI-1201 with pre-treatment 1
TBI-1201(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
 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
Experimental: High dose TBI-1201 with pre-treatment 1
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
 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
Experimental: High dose TBI-1201 with pre-treatment 2
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
 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
Experimental: TBI-1201 with pre-treatment 1 or 2
Arm1, 2 or 3, which is considered as optimal.
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Appearance of replication competent retrovirus by PCR [ Time Frame: 8 weeks ]
    Confirm no replication competent retrovirus observed

  3. Appearance of clonality by LAM-PCR [ Time Frame: 8 weeks ]
    Confirm no clonality is observed

  4. Kinetics of TBI-1201 in blood by realtime-PCR and flow cytometry [ Time Frame: 8 weeks ]
    Evaluate persistence and expansion of transferred TBI-1201


Eligibility Criteria
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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) , 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.
Contacts and Locations
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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): NCT02096614


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
Principal Investigator: Shinichi Kageyama, M.D., Ph.D. Mie University Hospital
More Information
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Responsible Party: Shinichi Kageyama, Professor, Mie University
ClinicalTrials.gov Identifier: NCT02096614    
Other Study ID Numbers: 1201-01
First Posted: March 26, 2014    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
Keywords provided by Shinichi Kageyama, Mie University:
Adoptive cell transfer
Cell therapy
Immunotherapy
MAGE-A4
Esophageal cancer
 Melanoma
Head and neck cancer
Ovarian cancer
TCR gene therapy
Additional relevant MeSH terms:
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Cyclophosphamide
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