Investigator Initiated Phase 1 Study of TBI-1201

NCT ID: NCT02096614

Last Updated: 2021-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2021-03-31

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low dose TBI-1201 with pre-treatment 1

TBI-1201(5\*10\^8) single-dose administration with pre-treatment of cyclophosphamide alone.

Group Type: EXPERIMENTAL

TBI-1201

Intervention Type: DRUG

TBI-1201(5\*10\^8 or 5\*10\^9) is administered.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201

High dose TBI-1201 with pre-treatment 1

TBI-1201(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide alone.

Group Type: EXPERIMENTAL

TBI-1201

Intervention Type: DRUG

TBI-1201(5\*10\^8 or 5\*10\^9) is administered.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201

High dose TBI-1201 with pre-treatment 2

TBI-1201(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.

Group Type: EXPERIMENTAL

TBI-1201

Intervention Type: DRUG

TBI-1201(5\*10\^8 or 5\*10\^9) is administered.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201

Fludarabine

Intervention Type: DRUG

Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1201 in combination with cyclophosphamide.

TBI-1201 with pre-treatment 1 or 2

Arm1, 2 or 3, which is considered as optimal.

Group Type: EXPERIMENTAL

TBI-1201

Intervention Type: DRUG

TBI-1201(5\*10\^8 or 5\*10\^9) is administered.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201

Fludarabine

Intervention Type: DRUG

Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1201 in combination with cyclophosphamide.

Interventions

TBI-1201

TBI-1201(5\*10\^8 or 5\*10\^9) is administered.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1201

Intervention Type: DRUG

Fludarabine

Fludarabine (20mg/m2 x 5 days Intravenous(IV)) is administered as pre-treatment medication of TBI-1201 in combination with cyclophosphamide.

Intervention Type: DRUG

Other Intervention Names

MAGE-A4-specific TCR gene transduced T lymphocytes; Endoxan; Fludara

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takara Bio Inc.

INDUSTRY

Sponsor Role: collaborator

Shionogi

INDUSTRY

Sponsor Role: collaborator

Fiverings Co., Ltd.

OTHER

Sponsor Role: collaborator

Statcom Co. Ltd.

UNKNOWN

Sponsor Role: collaborator

Mie University

OTHER

Sponsor Role: lead

Responsible Party

Shinichi Kageyama

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hiroshi Shiku, M.D., Ph.D.

Role: STUDY_CHAIR

Department of Immuno-Gene Therapy, Mie University, graduate School of Medicine

Shinichi Kageyama, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mie University Hospital

Locations

Mie University Hospital

Tsu, Mie-ken, Japan

Countries

Japan

Other Identifiers

1201-01

Identifier Type: -

Identifier Source: org_study_id