Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety: Incidence and severity of adverse events
研究概览
简要总结
This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (TLBL).
详细描述
The CARs consist of an anti-CD7 single-chain variable fragment（scFv）, a portion of the human CD137（4-1BB） molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy.
The Main research objectives:
To evaluate the safety and efficacy of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL
The Secondary research objectives:
To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL
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
- 2 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2 Guideline. Refractory T-ALL is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed T-ALL is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patients whose tumor burden >5% blasts, or who have persistent positive minimal residual disease (MRD), or have reappearance of extramedullary lesions are also considered eligible.
- •CD7-positive tumor (≥70% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory). tumors burden >5%,or MRD+， or new extramedullary lesions reappeared.
- •Life expectancy greater than 12 weeks
- •KPS or Lansky score≥60
- •oxygen saturation of blood>90%
- •Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal
- •Informed consent explained to, understood by and signed by patient/guardian.
排除标准
- •Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment)
- •Has an active GvHD;
- •Has a history of severe pulmonary function damaging;
- •With other tumors which is/are in advanced malignant and has/have systemic metastasis;
- •Severe or persistent infection that cannot be effectively controlled；
- •Presence of severe autoimmune diseases or immunodeficiency disease;
- •Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
- •Patients with HIV infection or syphilis infection;
- •Has a history of serious allergies to biological products (including antibiotics);
- •Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-
- •Presence of any symtomatic CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
- •Received allogeneic hematopoietic stem cell transplantation within 6 months;
- •Being pregnant and lactating or having pregnancy within 12 months;
- •Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.
结局指标
主要结局
Safety: Incidence and severity of adverse events
时间窗: First 1 month post CAR-T cells infusion
To evaluate the possible adverse events occurred within the first one month after CD7 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity
Efficacy: Remission Rate
时间窗: 3 months post CAR-T cells infusion
Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、partial remission(PR), No remission(NR), overall remission (OR)
次要结局
- duration of response (DOR)(24 months post CAR-T cells infusion)
- Efficacy: progression-free survival (PFS)(24 months post CAR-T cells infusion)
- Cytokine release(First 1 month post CAR-T cells infusion)
- Pharmacokinetics (PK) indicators:(Long time)
- Pharmacodynamic (PD) indicators:(First 1 month post CAR-T cells infusion)
- CAR-T proliferation(3 months post CAR-T cells infusion)