Clinical Study of Novel TLR2-Containing CAR-T Cells Targeting CD19 and CD22 for Refractory/Relapsed B-Cell Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 入组人数
- 60
- 主要终点
- ORR
研究概览
简要总结
The purpose of this clinical trial is to evaluate the safety and efficacy of CAR1922T2 T-cell therapy in participants with relapsed/refractory B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. Participants will receive a single infusion of CAR1922T2 T-cells and complete follow-ups over the next three years.
详细描述
Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the clonal proliferation of precursor lymphoid cells, with a cure rate of only 30-40% in adults through standardized chemotherapy. Non-Hodgkin's lymphoma (NHL) is a highly heterogeneous group of lymphatic and reticular neoplasms derived from the clonal malignant proliferation of lymphoid cells, with 30-40% of patients developing into refractory disease or relapsing after initial treatment. Although CAR-T cell therapy targeting CD19 has made significant progress in the treatment of patients with refractory/relapsed B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma, more than 50% of patients treated with CAR19 experience disease progression, which is related to the loss of CD19 on the cell surface. Therefore, our research team has developed a dual-specific CAR-T cell targeting both CD19 and CD22 to enhance the tumor-killing ability of CAR-T cells.
This clinical trial aims to evaluate the effectiveness and safety of CAR-T cell therapy targeting CD19 and CD22 (CAR1922T2 T cells) in participants with refractory/relapsed B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. After treatment with CAR1922T2 T cells, the effectiveness and safety of CAR1922T2 T-cell therapy for refractory/relapsed B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma will be assessed through clinical symptom evaluation, quality of life assessment, biomarker testing, laboratory testing, imaging evaluation, adverse event monitoring, and follow-up surveys.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. The patient or their legal guardian voluntarily participates and signs an informed consent form.
- •2.Age between 18-80 years old (inclusive), with no gender restrictions. 3.Diagnosed with acute B-cell acute lymphoblastic leukemia or non-Hodgkin's lymphoma according to the WHO 2016 classification.
- •4.CD19 or CD22 positivity confirmed by flow cytometry or histopathology. 5.Diagnosed with refractory/relapsed B-cell acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
- •6.Good major organ function:
- •Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤ 34.2 μmol/L;
- •Kidney function: Creatinine clearance rate (Cockcroft-Gault method) ≥ 60 mL/min;
- •Lung function: Oxygen saturation ≥ 95%, with no active pulmonary infection;
- •Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; no significant pericardial effusion, no clinically significant ECG abnormalities.
- •7.Women of childbearing age with negative urine/blood pregnancy test during screening and agree to use contraceptive measures for at least 1 year after infusion; male subjects with reproductive capacity must agree to use effective barrier contraceptive methods for at least 1 year after infusion.
- •8.ECOG score ≤
- •9.Life expectancy greater than 3 months.
排除标准
- •1.Women who are breastfeeding. 2.Patients with uncontrollable infectious diseases within 4 weeks before enrollment.
- •3.Active hepatitis B/C. 4.HIV-infected patients. 5.Patients with severe autoimmune diseases or immunodeficiency diseases. 6.Patients with allergic constitution, allergic to antibodies or cytokines and other large molecule biological drugs.
- •7.Patients who have participated in other clinical trials within 4 weeks before enrollment.
- •8.History of clinically significant central nervous system diseases: such as epilepsy, paralysis, aphasia, stroke, severe brain trauma, dementia, Parkinson's disease, cerebellar diseases, organic brain syndromes.
- •9.Patients with mental illness. 10.Patients with drug abuse/addiction. 11.Use of contraindicated medications.
- •. Steroids: Use of therapeutic doses of corticosteroids (defined as prednisone or equivalent >20 mg/day) within 7 days before leukocyte collection, or within 72 hours before CAR-T cell infusion targeting CD19 and CD
- •However, physiological replacement, topical, and inhaled corticosteroids are allowed.
- •. Chemotherapy: Received salvage chemotherapy within 2 weeks before leukocyte collection.
- •. Allogeneic cell therapy: Received donor lymphocyte infusion within 4 weeks before leukocyte collection.
- •. GVHD treatment: Received anti-GVHD treatment within 4 weeks before CAR-T cell infusion targeting CD19 and CD
- •. Use of alemtuzumab, or cladribine within 6 months before leukocyte collection, or use of chlorambucil or clofarabine within 3 months.
研究组 & 干预措施
Experimental Arm
Administer a single infusion of CAR1922T2 T cells to this group of patients following fludarabine plus cyclophosphamide (F+C) lymphodepletion, and conduct follow-up surveys at the required time points within three years post-infusion according to the visit schedule.
干预措施: CAR1922T2 T cells（Targeting CD19 and CD22 with CAR-T cells） (Biological)
结局指标
主要结局
ORR
时间窗: 3 years
The overall response rate (ORR) includes both complete response (CR) and partial response (PR), and uses the Clopper-Pearson method to calculate the two-sided 95% confidence interval.
次要结局
未报告次要终点