NCT04877080撤回1 期
Exploratory Study to Evaluate Efficacy and Safety of Fast Dual CAR-T Injection in CD19+ Refractory or Relapsed B Cell Non-Hodgkinlymphoma
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China0 个研究点开始时间: 2021年5月5日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Incidence of AE after Fast Dual CAR-T infusion
研究概览
简要总结
This is a single arm, open-label, single-center prospective study to determine the safety and efficacy of Fast Dual CAR-T cells in patients diagnosed with CD19+ refractory/relapsed B cell non-Hodgkinlymphoma (R/R B-NHL).
详细描述
The main aim of the study is to determine the safety and efficacy of Fast Dual CAR-T in R/R B-NHL. Fast Dual CAR-T is an autologous dual chimeric antigen receptor T-cell (CAR-T) therapy that targets CD19 and B-cell maturation antigen (BCMA). The study will include 15 subjects to receive Fast Dual CAR-T single infusion.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed: Diffuse Large B Cell Lymphoma (DLBCL), Transformation Follicular Lymphoma (TFL), Primary Mediastinal Large B Cell Lymphoma (PMBCL) and Mantle Cell Lymphoma (MCL), High-Grade B Cell Lymphoma (HGBL);
- •Refractory B-NHL: PD as the best response to normative first-line therapy (intolerance of first-line therapy is not included in this study) or SD as the best response to at least 4 courses of first-line therapy with duration no longer than 6 month from last therapy; or PD as the best response to the last therapy of second-line therapy and above,or SD as the best response to at least 2 courses of second-line therapy with duration no longer than 6 month from last therapy, or:
- •Relapsed B-NHL: Histopathology confirmed relapse after standard systemic and second-line therapy achieved CR, or histopathologically confirmed relapse within 1 year after autologous hematopoietic stem cell transplantation (Not limited by previous therapy);
- •Prior therapy must include anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and an anthracycline;
- •For individual with TFL, must have chemotherapy and the conform the above definition of relapse or refractory after transformation;
- •According to the 2014 Lugano therapy response standard, there should be at least one measurable tumor focus: the longest diameter of nodular lesions> 1.5 cm, and the longest diameter of extranodal lesions> 1.0 cm;
- •CD19 positive expression in tumor tissue biopsy;
- •Prior to apheresis, approved anti-B-NHL therapys such as systemic chemotherapy, systemic radiotherapy and immunotherapy have been completed for at least 2 weeks;
- •Eastern cooperative oncology group (ECOG) performance status of 0 to 1;
- •Life expectancy ≥12 weeks;
- •Absolute neutrophil count (ANC)≥ 1×10^9/L;
- •Platelet count≥50×10^9/L;
- •Absolute lymphocyte count (ALC)≥1×10^8/L;
- •Adequate organ function defined as:
- •Serum ALT/AST ≤2.5 ULN;
- •Creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min;
- •PT and APTT≤1.5 ULN
- •Total bilirubin ≤1.5 ULN;
- •Cardiac ejection fraction ≥50%, no pericardial effusion, no clinically significant ECG findings;
- •Baseline oxygen saturation >92% on room air;
- •Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis;
- •Female of childbearing age must agree to take effective contraceptive measures at least 1 year after infusion; Male with fertile partners must agree to use effective barrier contraceptive methods at least 1 year after infusion;
- •Understand and voluntarily sign the informed consent form.
排除标准
- •Diagnosis of other malignancy (except for cured non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, ductal carcinoma in situ, or other malignancies that have completely responsed for more than 5 years);
- •Severe mental disorders;
- •History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome;
- •History of allogeneic stem cell transplantation;
- •Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstableangina pectoris, or other clinically prominent heart disease within one year before enrollment.
- •Have any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, indwelling catheter, bile drainage tube or pleura / peritoneum / pericardial catheter), the use of dedicated central venous catheter is allowed;
- •Subjects with CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
- •History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
- •Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA;
- •Presence of fungal, bacterial, viral, or other infection that is uncontrolled;
- •Allergic subjects or subjects with severe allergic reactions to cyclophosphamide or fludarabine;
- •History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years;
- •History or diagnosis of pulmonary fibrosis;
- •Have received gene therapy or any other CAR-T treatment;
- •Have received any other drugs targeting CD19;
- •Subjects who received other clinical trial therapy within 4 weeks before participating in this trial, or the informed consent form was signed within the 5 half-life of the last administration in the other clinical trial (take longer time as standard);
- •Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan;
- •Subjects with comorbidities that require systemic corticosteroid therapy (≥5 mg/day of prednisone or an equivalent dose of other corticosteroids) or other immunosuppressive drugs within 6 months after study therapy according to the discretion of investigator;
- •Lactating women who are reluctant to stop breastfeeding;
- •Any other conditions defined by researcher that is inappropriate for the subject to be enrolled.
结局指标
主要结局
Incidence of AE after Fast Dual CAR-T infusion
时间窗: up to 24 weeks after Fast Dual CAR-T infusion
Incidence of adverse events after Fast Dual CAR-T infusion
次要结局
- ORR rate(12 weeks, 24 weeks after Fast Dual CAR-T infusion)
- OS(12 weeks, 24 weeks after Fast Dual CAR-T infusion)
- PFS(12 weeks, 24 weeks after Fast Dual CAR-T infusion)
- Changes in the concentration of cytokine IL-1, IL-2, IL-6, IL-10, TNF-α and IFN-γ.(Days 4, 7, 10, 14 and 28 after Fast Dual CAR-T infusion)
- Change of CAR Copies(Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after Fast Dual CAR-T infusion)
- Change of RCL in blood(Weeks 4, 12, 24 after Fast Dual CAR-T infusion)
- Change of CAR-T cell counts(Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after Fast Dual CAR-T infusion)
研究者
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