NCT06110208终止早期 1 期
Clinical Study to Evaluate the Safety and Preliminary Efficacy of CLL1 and CD38 Dual CAR-T Injection in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China1 个研究点 分布在 1 个国家目标入组 3 人开始时间: 2023年10月10日最近更新:
适应症
干预措施
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Dose limited toxicity (DLT);
研究概览
简要总结
This study is a single-center clinical study. The main purpose is an IIT clinical trial to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual CAR-T injection in r/r AML subjects . The included population were patients with relapsed and refractory acute myeloid leukemia (r/r AML) .
详细描述
Single-center clinical study. The main purpose is an IIT clinical trial to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual CAR-T injection in r/r AML subjects . The included population was patients with relapsed and refractory acute myeloid leukemia (r/r 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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-70 years old (including the critical value) when signing the informed consent form;
- •Diagnosed with acute myeloid leukemia (excluding APL) according to the World Health Organization 2016 criteria and relapsed and refractory AML according to the ELN2022 criteria;
- •Positive expression of CLL1 and/or CD38 in malignant cells must be detected by immunohistochemistry or flow cytometry (≥20 % );
- •If there are AEs caused by previous chemotherapy, it must be restored to CTCAE V5.0 grade 1;
- •Estimated survival time ≥3 months;
- •ECOG score 0 or 1 during screening period;
- •Hemoglobin ≥80g/L (have not received red blood cell transfusion within 7 days before screening, use of recombinant human erythropoietin is allowed);
- •Adequate organ functional reserve:
- •Alanine aminotransferase/aspartate aminotransferase ≤2.5× ULN (upper limit of normal value);
- •Serum total bilirubin ≤2× ULN, except for subjects with congenital bilirubinemia (for subjects with Gilbert syndrome, direct bilirubin needs to be ≤1.5× ULN);
- •Serum creatinine clearance >45mL/min (calculated according to the Cockcroft-Gault formula);
- •Left ventricular ejection fraction ≥35%;
- •Basic oxygen saturation in indoor air environment is ≥ 92 %
- •Ability to discontinue corticosteroids (dexamethasone ≥3 mg/day or other equivalent doses of steroids) starting on day -7 and continuing until 30 days after CAR-T cell infusion;
- •Women of childbearing age must have a negative pregnancy test for human chorionic gonadotropin (HCG) (immunofluorescence method) during the screening period and baseline period. Male subjects will need to agree not to donate sperm for at least one year after reinfusion. Males and sexual partners of childbearing potential agree to use highly effective contraceptive measures for at least 1 year after infusion;
- •Agree to perform follow-ups in accordance with the requirements of the protocol and informed consent form;
- •With the consent of the subject and the informed consent form voluntarily signed by the subject or his legal representative.
排除标准
- •Diagnosis of acute promyelocytic leukemia;
- •clinical trial investigational drugs or cell therapies within 2 weeks or 5 half-lives ;
- •Acute myeloid leukemia of unknown lineage ;
- •Those who have active graft-versus-host disease (GVHD) at the time of enrollment or develop active acute or chronic GVHD within 4 weeks after enrollment or require immunosuppressive drugs to treat GVHD;
- •There is an active infection;
- •Suffering from other malignant tumors (except non-melanoma skin cancer and in situ cervical cancer, bladder cancer, and breast cancer with a disease-free survival period of more than 5 years);
- •The subject has had a stroke or epilepsy within 6 months before signing the informed consent form;
- •The subjects' cardiac function showed the following conditions:
- •New York Heart Association (NYHA) class III or IV heart failure;
- •Myocardial infarction or coronary artery bypass grafting (CABG) occurred within 6 months before signing the informed consent form;
- •A history of clinically significant ventricular arrhythmia or syncope of unknown origin (not caused by vasovagal or dehydration);
- •Have a history of severe non-ischemic cardiomyopathy;
- •Cardiac dysfunction (left ventricular <35%) assessed by echocardiography or multiple gated acquisition scans, or other heart disease with clinical symptoms within 6 months before enrollment;
- •Active or previous central nervous system involvement, or clinically significant clinical manifestations of central nervous system involvement in subjects with acute myeloid leukemia ;
- •A positive virological test result for any of the following:
- •Human immunodeficiency virus antibodies (HIV antibodies);
- •Hepatitis C virus antibody (HCV antibody), those who are positive need to be tested for HCV-RNA, and those whose values are lower than the lower limit of the detection value can be enrolled;
- •HBsAg positive; or HBcAb positive; if HBcAb is positive, further testing of HBV DNA copy number is required . Those who are lower than the lower limit of the detection value can be enrolled;
- •Treponema pallidum antibodies (TPPA antibodies);
- •presence of pulmonary fibrosis;
- •Severe allergic history or allergic constitution;
- •The subject has undergone open injury or major surgery (referring to level III surgery and level IV surgery) within 2 weeks before signing the informed consent form, or plans to have surgery during the trial or within 2 weeks after reinfusion (excluding local anesthesia surgery) ;
- •for cyclophosphamide combined with fludarabine ;
- •Cannulae or drains other than central venous catheters;
- •Pregnant women, lactating women, or men who plan to give birth within 1 year of receiving treatment;
- •Any other circumstances that the researcher deems inappropriate for inclusion.
研究组 & 干预措施
AML subjects
Experimental
This study is a single-center clinical study. The main purpose is an IIT clinical trial to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual CAR-T injection in r/r AML subjects . The included population was patients with relapsed and refractory acute myeloid leukemia (r/r AML) .
干预措施: CLL1 and CD38 dual-target CAR-T injection (Drug)
结局指标
主要结局
Dose limited toxicity (DLT);
时间窗: 28 days after CAR-T infusion
Dose limited toxicity (DLT);
Adverse events (AE)
时间窗: 48 weeks after CAR-T infusion
• Adverse events (AE): CTCAE version 5.0 standards will be used for rating
次要结局
- • Partial response rate (PRR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Median bone marrow blast percentage decline;(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • CR with incomplete hematologic recovery rate (CRiR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Overall response rate (ORR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Overall complete response rate (CRR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Event-free survival (EFS);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Relapse-free survival (RFS);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Overall survival (OS);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Expansion and persistence of CAR-T cells (CAR copy number and CAR - T cell number)(Days 4, 7, 10, 14 ,21,28 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion)
- • The proportion of subjects with RCL detected in peripheral blood and the insertion site of CAR-T cell lentivirus within 15 years after the infusion of CLL1 and CD38 dual-target CAR-T injection.(within 15 years after the infusion of CLL1 and CD38 dual CAR-T injection)
- • Morphologic leukemia-free state rate (MLFSR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • The proportion of patients who achieved complete remission (CR) who tested negative for MRD (MRD-rate);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • Duration of response (DOR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
- • CR with partial hematologic recovery rate (CRhR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
研究者
研究点 (1)
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