Clinical trial NCT02366546: Investigator Initiated Phase 1 Study of TBI-1301
Official title: Multi-center, Investigator Initiated Phase 1 Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Adoptive cell transfer
Cell therapy
Immunotherapy
NY-ESO-1
Esophageal cancer
Melanoma
Head and neck cancer
Ovarian cancer
Synovial sarcoma
TCR gene therapy
Lead sponsor: Mie University
Sponsor class: OTHER
Collaborators: name: Takara Bio Inc.
name: Shionogi
name: Fiverings Co., Ltd.
name: Statcom Co. Ltd.
First posted: 2015-02-19
Enrollment: 9
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence and grade of adverse events (CTCAE)
timeFrame: 4 weeks
measure: Appearance of replication competent retrovirus by PCR
timeFrame: 4 weeks
measure: Appearance of clonality by LAM-PCR
timeFrame: 4 weeks
measure: Kinetics of TBI-1301 in blood by realtime-PCR
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
Study officials:
affiliation: Department of Immuno-Gene Therapy, Mie University, Graduate School of Medicine Mie University Hospital
name: Hiroshi Shiku, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Department of Immuno-Gene Therapy, Mie University, Graduate School of Medicine Mie University Hospital
name: Shinichi Kageyama, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.