This is an Open, Single-arm, Clinical Study to Evaluate the Efficacy and Safety of Anti-CD7/CD5 CAR-T Cells in the Treatment of Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL), ETP-ALL, and Lymphoblastic Lymphoma (TLBL).
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Disease response to CD7/CD5 CAR T cells
研究概览
简要总结
Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may be the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of Sequential CAR-T Cells Targeting CD5/CD7 in patients with patients with relapsed or refractory T-ALL/LBL/ETP-ALL. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.
详细描述
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 are 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 Sequential CAR-T Cells Targeting CD5/CD7 to examine the safety and, possibly the efficacy of CD5 CAR T-Cells in CD5+ CD7+ 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
盲法说明
Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.
入排标准
- 年龄范围
- 2 Years 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent; Patients volunteer to participate in the clinical trial;
- •Diagnosis is mainly based on the World Health Organization (WHO) 2008;
- •Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%;
- •Leukemic blast cells express CD7/CD5 (CD7 OR CD5 positive by flow cytometry or immunohistochemistry ≥70%);
- •The expected survival period is greater than 12 weeks;
- •ECOG score ≤2;
- •Age 2-60 years old;
- •HGB≥70g/L (can be transfused);
- •Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.
排除标准
- •Patients declining to consent for treatment
- •Prior solid organ transplantation
- •One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV;
- •History of severe pulmonary dysfunction diseases;
- •Severe infection or persistent infection cannot be effectively controlled;
- •Severe autoimmune disease or congenital immunodeficiency;
- •Active hepatitis;
- •Human immunodeficiency virus (HIV) infection;
- •Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).
研究组 & 干预措施
Sequential CAR-T Cells Targeting (CD5/CD7 CAR T cells, chemotherapy)
Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD5/CD7 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD5/CD7 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD5/CD7 CAR T cells.
干预措施: CD5/CD7 CAR-T (Biological)
结局指标
主要结局
Disease response to CD7/CD5 CAR T cells
时间窗: 1 year
The disease response to CD7/CD5 CAR T cells is evaluated by bone marrow biopsy and aspirate within 1 year after CAR infusion. The proportion of subjects receiving CD7/CD5 CAR T infusion to 1) morphological remission (blasts \<5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable).
The number and incidence of adverse events after CD7/CD5 CAR infusion.
时间窗: 28 days
Evaluation of all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR-T infusion
次要结局
未报告次要终点