Clinical Study on the Efficacy and Safety of Functionally Optimized CD33 CAR-T Cells (FO33 CAR-T) Therapy Targeting CD33-Positive Recurrent/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 主要终点
- Evaluate the safety of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
研究概览
简要总结
Relapsed/refractory acute myeloid leukemia (AML) currently lacks effective CAR-T therapy products due to the absence of specific target antigens. Most AML antigens are frequently expressed in normal hematopoietic stem/progenitor cells (HSPCs) or healthy organ tissues, thereby increasing the risks of target toxicity and non-neoplastic toxicity. CD33 is expressed in leukemia cells from over 80% of AML patients. Compared to other targets such as CLL-1 and CD123, CD33 typically exhibits higher expression levels across various AML subtypes, reducing the risk of treatment failure and relapse caused by tumor antigen escape, making it an ideal therapeutic target for AML. However, conventional CD33 CAR-T therapies have demonstrated suboptimal efficacy in clinical trials and face challenges such as toxicity and insufficient expansion. To further investigate the safety and efficacy of CAR-T therapy for AML, our center has initiated a clinical study on functionally optimized CD33 CAR-T (FO33 CAR-T) cell therapy for refractory/refractory AML.
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
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Subjects diagnosed with refractory/recurrent acute myeloid leukemia (excluding M3) who meet any of the following criteria:
- •Relapse: Recurrence of leukemia cells in peripheral blood or ≥5% blast cells in bone marrow after complete remission (CR) of AML (excluding other causes such as bone marrow regeneration following consolidation chemotherapy), or extramedullary leukemia infiltration.
- •Refractory: First-time cases unresponsive to two cycles of standard therapy; relapse within 12 months after consolidation therapy following CR; relapse after 12 months without response to conventional chemotherapy; two or more relapses; persistent extramedullary leukemia.
- •2. During enrollment screening, bone marrow flow cytometry must demonstrate a CD33+ expression rate of ≥80% in leukemia cells and/or pathological immunohistochemical confirmation of CD33+ extramedullary lesions;
- •Estimated survival duration exceeding 3 months as of the date of informed consent signing;
- •Participants with Eastern Cooperative Oncology Group (ECOG) physical status scores ranging from 0 to 2;
- •Age range of 14 years ≤ ≤ 75 years, inclusive, with no gender restriction;
- •Hemoglobin (HGB) level ≥70 g/L with transfusion capability;
- •Liver/kidney function and cardiopulmonary function meeting the following criteria:
- •Creatinine ≤1.5×ULN;
- •Left ventricular ejection fraction ≥50%;
- •Blood oxygen saturation>90%;
- •Total bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN;
- •Acceptance of autologous CART cells with peripheral blood tumor burden ≤ 30%;
- •The subject or guardian understands and signs the informed consent form.
排除标准
- •1. Presence of one of the following cardiac criteria: atrial fibrillation; myocardial infarction (MI) within the past 12 months; prolonged QT syndrome or secondary QT prolongation as determined by the investigator. Echocardiographic left ventricular systolic fraction (LVSF) <30% or left ventricular ejection fraction (LVEF) <50%; clinically significant pericardial effusion; New York Heart Association (NYHA) class III or IV heart failure (confirmed by echocardiography within 12 months after treatment).
- •2. Active graft-versus-host disease (GVHD);
- •History of severe pulmonary dysfunction;
- •Concurrent other progressive malignancies;
- •Concurrent severe or persistent infections that cannot be effectively controlled;
- •Concurrent severe autoimmune diseases or congenital immunodeficiency;
- •Active hepatitis (HBV-DNA ≥ 500 IU/ml with abnormal liver function or HCV antibody [HCV-Ab] positivity, HCV-RNA exceeding the detection limit of analytical methods with abnormal liver function);
- •Human immunodeficiency virus (HIV) infection or syphilis infection;
- •History of severe allergic reactions to biological products (including antibiotics);
- •Presence of central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, or cerebellar diseases;
- •Female patients in pregnancy or lactation, or planning pregnancy within 12 months;
- •Situations where investigators consider may increase subject risk or interfere with trial outcomes.
研究组 & 干预措施
Functionally optimized CD33 CAR-T
干预措施: Functionally optimized CD33 CAR-T (Biological)
结局指标
主要结局
Evaluate the safety of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
时间窗: up to one month after the CAR-T infusion
the incidence and severity of immune therapy related toxic reactions (irAEs)
Evaluate the effcacy of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
时间窗: one month and three month after the CAR-T infusion
CR rate on M1 and M3
次要结局
- Cell pharmacokinetics Dynamic indicators(Day7, Day10, Day14, Day28 after the CAR-T infusion)
- long-term efficacy(up to one year after the CAR-T infusion)
研究者
Qi deng
Chief Physician
Tianjin First Central Hospital