Investigator Initiated Phase 1 Study of TBI-1301

NCT ID: NCT02366546

Last Updated: 2018-10-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31

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.

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.

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-1301 with pre-treatment 1

TBI-1301(5\*10\^8) single-dose administration with pre-treatment of cyclophosphamide alone.

Group Type: EXPERIMENTAL

TBI-1301

Intervention Type: DRUG

TBI-1301(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-1301.

High dose TBI-1301 with pre-treatment 1

TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide alone.

Group Type: EXPERIMENTAL

TBI-1301

Intervention Type: DRUG

TBI-1301(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-1301.

High dose TBI-1301 with pre-treatment 2

TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.

Group Type: EXPERIMENTAL

TBI-1301

Intervention Type: DRUG

TBI-1301(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-1301.

Fludarabine

Intervention Type: DRUG

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

TBI-1301 with pre-treatment 1 or 2

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

Group Type: EXPERIMENTAL

TBI-1301

Intervention Type: DRUG

TBI-1301(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-1301.

Fludarabine

Intervention Type: DRUG

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

Interventions

TBI-1301

TBI-1301(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-1301.

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Other Intervention Names

NY-ESO-1-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)

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.

• 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 Mie University Hospital

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

Role: PRINCIPAL_INVESTIGATOR

Department of Immuno-Gene Therapy, Mie University, Graduate School of Medicine Mie University Hospital

Locations

Mie University Hospital

Tsu, Mie-ken, Japan

Countries

Japan

References

Ishihara M, Kitano S, Kageyama S, Miyahara Y, Yamamoto N, Kato H, Mishima H, Hattori H, Funakoshi T, Kojima T, Sasada T, Sato E, Okamoto S, Tomura D, Nukaya I, Chono H, Mineno J, Kairi MF, Diem Hoang Nguyen P, Simoni Y, Nardin A, Newell E, Fehlings M, Ikeda H, Watanabe T, Shiku H. NY-ESO-1-specific redirected T cells with endogenous TCR knockdown mediate tumor response and cytokine release syndrome. J Immunother Cancer. 2022 Jun;10(6):e003811. doi: 10.1136/jitc-2021-003811.

Reference Type: DERIVED

PMID: 35768164 (View on PubMed)

Other Identifiers

1301-01

Identifier Type: -

Identifier Source: org_study_id