Multi-center, Investigator Initiated Phase 1 Study of MAGE-A4 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Incidence and grade of adverse events (CTCAE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed solid tumors
- •Solid tumor, which is unresectable , refractory to standard therapy (chemotherapy, radiotherapy, etc) , metastatic or recurrent
- •HLA-A*24:02 positive
- •MAGE-A4-expression by PCR or immunohistochemistry
- •ECOG Performance Status, 0 or 1
- •Age >20 years on consent
- •No treatment (surgery, chemotherapy, radiotherapy, etc.) and expected sufficient recovery from the treatment at the time of the lymphocytes collection for gene transfer.
- •Life expectancy >= 16 weeks after consent
- •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
- •Ability to understand the study contents and to give a written consent at his/her free will.
排除标准
- •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
- •Serious hypersensitivity
- •Tumor cell invasion into CNS
- •Active multiple cancer
- •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.
- •Positive for antibodies against HIV or HTLV-1
- •Left Ventricular Ejection Fraction (LVEF): =< 50％
- •Percutaneous Oxygen saturation: < 94％
- •History of hypersensitivity reactions to bovine or murine derived substances.
- •History of hypersensitivity reaction to drugs used in this study
- •Psychological disorder or drug dependency which may have impact on the consent.
- •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
- •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.
研究组 & 干预措施
Low dose TBI-1201 with pre-treatment 1
TBI-1201(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
干预措施: TBI-1201 (Drug)
Low dose TBI-1201 with pre-treatment 1
TBI-1201(5*10^8) single-dose administration with pre-treatment of cyclophosphamide alone.
干预措施: Cyclophosphamide (Drug)
High dose TBI-1201 with pre-treatment 1
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
干预措施: TBI-1201 (Drug)
High dose TBI-1201 with pre-treatment 1
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide alone.
干预措施: Cyclophosphamide (Drug)
High dose TBI-1201 with pre-treatment 2
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
干预措施: TBI-1201 (Drug)
High dose TBI-1201 with pre-treatment 2
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
干预措施: Cyclophosphamide (Drug)
High dose TBI-1201 with pre-treatment 2
TBI-1201(5*10^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
干预措施: Fludarabine (Drug)
TBI-1201 with pre-treatment 1 or 2
Arm1, 2 or 3, which is considered as optimal.
干预措施: TBI-1201 (Drug)
TBI-1201 with pre-treatment 1 or 2
Arm1, 2 or 3, which is considered as optimal.
干预措施: Cyclophosphamide (Drug)
TBI-1201 with pre-treatment 1 or 2
Arm1, 2 or 3, which is considered as optimal.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Incidence and grade of adverse events (CTCAE)
时间窗: 8 weeks
Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
Appearance of replication competent retrovirus by PCR
时间窗: 8 weeks
Confirm no replication competent retrovirus observed
Appearance of clonality by LAM-PCR
时间窗: 8 weeks
Confirm no clonality is observed
Kinetics of TBI-1201 in blood by realtime-PCR and flow cytometry
时间窗: 8 weeks
Evaluate persistence and expansion of transferred TBI-1201
次要结局
未报告次要终点