A Phase I Study of CD5 CAR-T for Refractory/Relapsed CD5+ T-ALL Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 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 a phase I, interventional, single arm, open label, clinical study to evaluate the safety and tolerability of CD5 CAR-T cells in refractory/relapsed CD5+ T-ALL patients who have no available curative treatment options.
详细描述
T-acute lymphoblast leukemia (T-ALL) is a neoplastic lymphoid leukemia characterized by the proliferation of immature precursor T cells. The combined chemotherapy has significantly improved the prognosis of T-acute lymphoblast leukemia/lymphoma. However, once the disease appears to be relapsed/refractory, there is limited treatment options, and the overall prognosis is extremely poor. Therefore, exploring safe and effective treatments is a critical unmet medical need. The patients will receive infusion of CAR T-cells targeting CD5 to examine the safety and, possibly the efficacy of CD5 CAR T-Cells in CD5+ relapsed or refractory acute 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
- 1 Year 至 18 Years（Child, 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) 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;
- •CD5-positive tumor (≥70% CD5 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;
- •Aged 1 to 18 years (including 18 years old);
- •Eastern Cooperative Oncology Group (ECOG) score 0-2;
- •Life expectancy greater than 12 weeks;
- •Oxygen saturation of blood>90%;
- •Total bilirubin (TBil) ≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 × upper limit of normal;
- •Informed consent explained to, understood by and signed by patient/guardian.
排除标准
- •Intracranial hypertension or brain consciousness disorder;
- •Has an active GvHD;
- •Has a history of severe pulmonary function damaging;
- •With other tumors which is/are in advanced malignant stage 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)-6;
- •Presence of any symptomatic 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 risk 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 following CD5 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity.
次要结局
- Duration of remission (DoR)(1 year)
- Event free survival within 1 year(1 year)
- Efficacy: Remission Rate(1 months post CAR-T cells infusion)
- Best overall response (BOR)(1 months)