A Multicenter Phase I/II Study for Relapsed or Refractory CD19+ B-acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 21
- 试验地点
- 11
- 主要终点
- Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Evaluate the safety (P-I), pharmacokinetics and anti-tumor effect of immunotherapy of autologous T cells genetically modified to express anti-CD19 chimeric antigen receptor (CAR) (TBI-1501) for relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia.
详细描述
Enroll patients after confirming eligibility. Following enrollment, peripheral blood mononuclear cells and blood plasma will be obtained from each subject by apheresis to start the manufacturing of TBI-1501.
Before TBI-1501 administration, it is necessary to pass the quality tests. Subject will be hospitalized from Day -3 to Day 28, and administered Cyclophosphamide (1,000 mg/m2/day×2 days) on Day -3 and Day -2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In phase-1 study, patients must be ≥ 18 years of age. In phase-2 study, patients must be ≥ 16 years of age.
- •Patients with relapse or refractory CD19+ acute B-cell lymphoblastic leukemia
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
- •Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc), as defined below
- •Total bilirubin level ≤1.5xULN (Upper limit of normal)
- •AST(GOT)/ALT(GPT) level ≤5.0xULN
- •Serum creatinine ≤2.0mg/dL
- •SpO2 ≧ 92%
- •LVEF ≥50%
- •Patients must be able to understand and willing to sign a written informed consent document (for patients <20 years of age their legal guardian must give informed consent).
排除标准
- •White blood cell counts ≧ 50,000/uL
- •Received expected antitumor therapy (chemotherapy or radiation therapy, etc) within 2 weeks.
- •Received HSCT within 12 weeks before enrollment.
- •Under treatment for GVHD.
- •lymphocytes except for blasts ≦ 500/uL
- •Presence of active CNS-3
- •Concurrent use of systemic steroids or immunosuppressive agents (except for replacement therapy and local administration. e.g. inhalation, application and so on).
- •HBs Ag positive ,or either HBc Ab positive or HBs positive with HBV-DNA > 1.3LogIU/ml
- •Presence of active hepatitis C infection
- •HIV Ab or anti-HTLV-1 Ab positive
- •History of allergy about component of investigational product or animal(cattle and/or mouse)-derived additives
- •Hypersensitivity to antibiotics.
- •Presence of symptomatic cardiac arrhythmias or serious heart disease.
- •Presence of another malignant tumor.
- •Psychiatric disorder, alcohol addiction or drug addiction that affects the ability of informed consent.
- •Active or serious infection.
- •Both men and women who have generative functions, and who cannot agree with using contraceptive devices from the day of the consent to the end of study.
- •Pregnant or lactating women.
- •Any other patients judged by the investigators to be inappropriate for the study.
研究组 & 干预措施
Dose Level -1 to 2
0.3 to 3 x 10^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide.
cohort -1: 3×10^5 cells/kg cohort 1: 1×10^6 cells/kg cohort 2: 3×10^6 cells/kg.
干预措施: TBI-1501 (Biological)
结局指标
主要结局
Phase-I portion: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: One year
Adverse event (frequency, seriousness, duration, causality, severity, classification), mortality, severe adverse event, discontinuation due to adverse event.
Phase-II portion: Anti-tumor effect (CR+CRi rate)
时间窗: 56 days
Complete Remission (CR)+Complete Remission with Incomplete Blood Count Recovery (CRi) , as determined by assessments of peripheral blood and bone marrow.
次要结局
未报告次要终点