Clinical Study of Anti-CD1a CAR-T in the Treatment of Relapsed Refractory Acute T-lymphoblastic Leukemia/Lymphoblastic Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
To evaluate the efficacy and safety of anti-CD1a CAR-T in the treatment of relapsed refractory acute T-lymphoblastic leukemia/lymphoblastic lymphoma.
详细描述
Acute T-lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is a highly heterogeneous hematological malignancy usually associated with genetic alterations/mutations in transcription factors that are major regulators of hematopoietic stem/progenitor cell homeostasis and T cell development. 70% of patients develop mass with myeloid invasion and other leukemia symptoms.
CD1a, a transfer membrane glycoprotein, is a cell surface antigen present on cortical T-ALL cells. It is present in 40% of T-ALL cases. Specific expression of this antigen has also been observed in developing cortical thymus cells. It was also slightly expressed in langerhans cells, digital dendritic cells, B lymphocytes and gastrointestinal epithelial cells. CD1a4 was not expressed in CD34+ progenitor cells or T cells during ontogeny. This property of CD1a makes it a suitable target antigen whose targeting minimizes the possibility of non-tumor toxicity.
This study intends to treat r/r CD1a+T-ALL/LBL with CD1a CAR-T to observe its safety and efficacy.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients or their legal guardians voluntarily participate and sign the informed consent;
- •Male or female patients aged 18-70 years (including 18 and 70 years);
- •The patient was diagnosed with CD1a+ acute T lymphoblastic leukemia/lymphoblastic lymphoma by pathology or flow cytometry, and had no effective treatment options at present, such as chemotherapy or hematopoietic stem cell transplantation after recurrence; Alternatively, the patient voluntarily chooses to administer antiCD1a-CAR T cells as salvage therapy. Inclusion criteria
- •Patients or their legal guardians voluntarily participate and sign the informed consent;
- •Male or female patients aged 18-70 years (including 18 and 70 years);
- •The patient was diagnosed with CD1a+ acute T lymphoblastic leukemia/lymphoblastic lymphoma by pathology or flow cytometry, and had no effective treatment options at present, such as chemotherapy or hematopoietic stem cell transplantation after recurrence; Alternatively, the patient voluntarily chooses to administer antiCD1A-CAR T cells as salvage therapy.
- •The following two categories are included:
- •(1) CD1a+T lymphoblastic lymphoma (T-LBL); (2) CD1a+ acute T-lymphoblastic leukemia (T-ALL).
- •There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable;
- •Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable;
- •Patients with high risk factors;
- •Relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy.
- •Measurable or evaluable lesions;
- •The patient's main tissues and organs function well:
- •Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L;
- •Renal function: creatinine < 220 μmol/L;
- •Lung function: indoor oxygen saturation ≥95%;
- •Cardiac function: left ventricular ejection fraction (LVEF) ≥40%.
- •The patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss);
- •The patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion;
- •Patients with ECOG score ≤2 and expected survival time ≥3 months.
- •The following two categories are included:
- •(1) CD1a+T lymphoblastic lymphoma (T-LBL); (2) CD1a+ acute T-lymphoblastic leukemia (T-ALL).
- •There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable;
- •Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable;
- •Patients with high risk factors;
- •Relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy.
- •Measurable or evaluable lesions;
- •The patient's main tissues and organs function well:
- •Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L;
- •Renal function: creatinine < 220 μmol/L;
- •Lung function: indoor oxygen saturation ≥95%;
- •Cardiac function: left ventricular ejection fraction (LVEF) ≥40%.
- •The patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss);
- •The patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion;
- •Patients with ECOG score ≤2 and expected survival time ≥3 months.
排除标准
- •Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding;
- •Men or women who have planned to become pregnant within the last 1 year;
- •The patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment;
- •Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment;
- •Active hepatitis B/C virus;
- •Hiv-infected patients;
- •Suffering from a serious autoimmune disease or immunodeficiency disease;
- •The patient is allergic to antibodies, cytokines and other macromolecular biological drugs;
- •The patient had participated in other clinical trials within 6 weeks prior to enrollment;
- •Systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
- •Suffers from mental illness;
- •The patient has substance abuse/addiction;
- •According to the researchers judgment, the patient had other conditions that were not suitable for inclusion.
结局指标
主要结局
Objective response rate
时间窗: From 2 weeks to 1 year.
CR+PR
Progression-free survival
时间窗: From 2 weeks to 1 year.
The time between treatment and observation of disease progression or death from any cause.
Event-free survival
时间窗: From 2 weeks to 1 year.
The time from the start of CAR-T infusion to the occurrence of any event.
overall survival
时间窗: From 2 weeks to 1 year.
The time interval between patient infusion of CAR-T and death from any cause or the end of follow-up.
次要结局
- Characteristics of lymphocyte reduction in subjects(From 2 weeks to 1 year.)
- Characterization of the level of CAR T cell expansion in subjects over time(From 2 weeks to 1 year.)
- Duration of CAR T cells in subjects(From 2 weeks to 1 year.)