A Clinical Study of Humanized CD19 CAR-T Cells With TLR2 for the Treatment of Adult Patients With Naive B-Cell Acute Lymphoblastic Leukemia/Lymphoma Who Are Intolerant to Intensive Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 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 tolerability and safety of humanized CD19 CAR-T therapy with TLR2 in adult patients with acute B lymphoblastic leukemia/lymphoma who cannot tolerate intense chemotherapy at initial treatment. Participants will receive a single infusion of CD19 CAR-T and complete follow-ups over the next three years.
详细描述
Objective
To evaluate the tolerability and safety of humanized CD19 CAR-T therapy with TLR2 in adult patients with acute B lymphoblastic leukemia/lymphoma who cannot tolerate intense chemotherapy at initial treatment. Secondary objective: To evaluate the efficacy and cytodynamics of humanized CD19 CAR-T therapy with TLR2 in adult acute B lymphoblastic leukemia/lymphoma who cannot tolerate intense chemotherapy at initial treatment.
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
- •Newly treated patients with acute B-lymphocytic leukaemia/lymphoma who are clinically determined to be unable to tolerate strong chemotherapy;
- •age 18-80 years old (including boundary value), both men and women can;
- •The physical status of the American Eastern Cancer Collaboration Group (ECOG) was 0~2 points;
- •Positive CD19 confirmed by flow cytometry and/or histopathology;
- •The expected survival period from the date of signing the informed consent form is more than 3 months.；
- •women of childbearing age screening period human chorionic gonadotropin (HCG) test negative, and Consent to use contraception for at least 1 year after the infusion; A man whose partner is fertile Subjects must agree to use an effective barrier contraceptive method for at least 1 year after the infusion；
- •the patient's main tissues and organs function well: (1) Liver function: ALT/AST<3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L; (2) Renal function: creatinine clearance (Cockcroft-Gault method) ≥60mL/min; (3) Lung function: blood oxygen saturation ≥95%, and no active lung infection; (4) Cardiac function: left ventricular ejection fraction (LVEF) ≥50%; No large number of pericardium was found Fluid accumulation, no clinically significant electrocardiogram abnormalities；
排除标准
- •severe cardiac insufficiency, left ventricular ejection fraction <50%;
- •have a history of severe lung function impairment;
- •Combined with other advanced malignant tumors;
- •Had severe infection within 4 weeks before enrollment and could not be effectively controlled;
- •suffering from serious autoimmune diseases or immune deficiency diseases;
- •active hepatitis (HBV DNA quantitative > 500IU/ml] or HCV ribose Nucleic acid [HCVRNA] test positive);
- •human immunodeficiency virus (HIV) infection or known to have acquired immunodeficiency syndrome Co-syndrom (AIDS), or syphilis infection;
- •Have a history of severe allergy to biological products (including antibiotics), antibodies or cytokines Allergy to macromolecular biological drugs;
- •Acute graft-versus-host reactions were still present one month after immunosuppressant discontinuation Patients with allogeneic hematopoietic stem cell transplantation (GvHD);
- •in the pregnancy period (urine/blood pregnancy test positive) or breastfeeding women; nearly Men or women who plan to conceive within 1 year; Not guaranteed to be taken within 1 year after enrollment Effective contraception (condoms or contraceptives, etc.);
- •History of clinically significant central nervous system diseases, such as epilepsy, paresis, and loss Speech, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic Cerebral syndrome;
- •Suffering from mental illness;
- •The patient has substance abuse/addiction;
- •Use of banned drugs. (1). Hormones: within 7 days before leukocyte collection, or within 72 hours before CD19CAR-T administration A past therapeutic dose of corticosteroid (defined as prednisone or equivalent > 20mg/day) Days). However, the use of physiological substitutes, topical and inhaled steroids is permitted. (2) Chemotherapy: rescue chemotherapy was received within 2 weeks before white blood cell collection. (3) Allogeneic cell therapy: donor lymphocytes were received within 4 weeks before white blood cell collection Infusion. (4).GVHD treatment: Anti-GVHD received within 4 weeks prior to CD19CAR T cell infusion Heal. (5) Alenzumab was used within 6 months before white blood cell collection, or chlorine was used within 3 months Farabine or cladobine.
研究组 & 干预措施
Experimental Arm
Administer a single infusion of humanized CD19 CAR-T Cells with TLR2 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: humanized CD19 CAR-T Cells with TLR2 (Biological)
结局指标
主要结局
ORR
时间窗: 3 years
Objective response rates (ORR), including CR and PR, were analyzed by Clopper-Pearson distribution with bilateral 95% confidence intervals. For progression-free survival (PFS), Kaplan-Meier method was used to estimate the survival curve. Overall survival: the time from cell retransfusion until death from any cause.
次要结局
未报告次要终点
研究者
Li Yuhua
professor
Zhujiang Hospital