Clinical Study of ssCART-19 Cells in Patients With CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed or refractory acute lymphoblastic leukemia.
详细描述
This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed or refractory acute lymphoblastic leukemia.
Primary objectives:
Determine the safety and tolerability of ssCART-19 cells in patients with refractory or relapsed acute lymphoblastic leukemia.
Secondary objectives:
- Observe the anti-tumor response of ssCART-19 cells to refractory or relapsed acute lymphoblastic leukemia.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed or refractory acute lymphoblastic leukemia (ALL):(1)Any Relaps after first remission OR (2)Any BM relapse after allogeneic SCT and must be ≥ 3 months from SCT at the time of ssCART-19 infusion OR (3)failed to reach CR after 2 cycles of induction chemotherapy regimen OR (4)Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated
- •CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry
- •Bone marrow with ≥ 5% lymphoblasts by morphologic assessment
- •Adequate organ function defined as:(1)left ventricular ejection fraction ≥ 50% by echocardiogram；(2)creatinine ≤ 1.6mg/dl；(3)ALT and AST≤3 times the ULN for age, total bilirubin ≤ 2.0mg/dl；(4)Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air
- •Informed consent is signed by the subject
- •Age 18 to 65
- •Fertility of men, to ensure that sexual partners can effectively contraception; Women with fertility use effective contraceptive measures and agree to use contraceptive measures throughout the study period
- •Qualified T cell amplification
- •Eastern cooperative oncology group (ECOG) performance status of 0 to 1
- •Vascular conditions for apheresis
- •The estimated survival time is more than 3 months
排除标准
- •Isolated extra-medullary disease relapse
- •Combined with other malignant tumors
- •Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other antiCD19 therapy
- •Has had immunosuppressants or hormones within 2 weeks before signing informed consent, or plan to use immunosuppressants or hormones after signing informed consent
- •Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive, hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of detection, hepatitis C antibody (HCV-Ab) positive, anti-treponemia pallidum antibody (TP-Ab) positive, EBV-DNA, and CMV-DNA copies being more than the lower limit of detection
- •Has uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infections
- •Infected with HIV, syphilis or COVID-19
- •Has a history of severe immediate hypersensitivity to aminoglycosides
- •Has past or present CNS diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases or any CNS-related autoimmune diseases
- •Has undergone cardiac angioplasty or stent implantation within 12 months before signing informed consent, or having a history of myocardial infarction, unstable angina pectoris or other clinically significant heart diseases
- •With primary immunodeficiency
- •Has had severe immediate hypersensitivity reaction to any drug to be used in this study
- •Has had treat with live vaccine within 6 weeks prior to screening
- •Pregnant or lactating women
- •Has active autoimmune diseases
- •Has active acute or chronic graft-versus-host disease (GVHD) before signing informed consent
- •Patient has an investigational medicinal product within 3 months before signing informed consent
- •Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator
研究组 & 干预措施
ssCART-19 Cells
Route of administration: Intravenous injection.
Lymphodepletion conditioning:
Lymphodepletion will be conducted several days prior to ssCART-19 cells infusion.
A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: ssCART-19 Cells (Genetic)
ssCART-19 Cells
Route of administration: Intravenous injection.
Lymphodepletion conditioning:
Lymphodepletion will be conducted several days prior to ssCART-19 cells infusion.
A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: Fludarabine (Drug)
ssCART-19 Cells
Route of administration: Intravenous injection.
Lymphodepletion conditioning:
Lymphodepletion will be conducted several days prior to ssCART-19 cells infusion.
A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: 28 days
Determine the safety and tolerability of ssCART-19 in patients with refractory or relapsed acute lymphoblastic leukemia. Safety measures include adverse events as assessed by CTCAE v5.0.
次要结局
- Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)(3 months)
- Duration of remission (DOR)(24 months)
- Progression-free Survival (PFS)(24 months)
- Overall survival (OS)(24 months)