NCT06219239招募中不适用
Evaluation of the Safety and Efficacy of KL003 Gene Therapy in Patients With Transfusion-dependent β-thalassemia With No Conditioning Regimen
Institute of Hematology & Blood Diseases Hospital, China1 个研究点 分布在 1 个国家目标入组 3 人开始时间: 2024年1月4日最近更新:
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- The number, frequency and severity of adverse events (AE) after reinfusion of KL003 drug products
研究概览
简要总结
This is a non-randomized, open-label, single-dose study. The aim of this study is to evaluate the safety and efficacy of the treatment with lentiviral vector encoding βA-T87Q-globin gene transduced autologous hematopoietic stem cells transfusion in subjects with transfusion-dependent β-thalassemia.
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
- 3 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female age between 3-35 years
- •Diagnosis of transfusion-dependent β-thalassemia and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years
- •Documented baseline, or pretransfusion, Hb level≤7 g/dL
- •Karnofsky performance status ≥70 for subjects≥16 years of age; Lansky performance status of ≥70 for subjects<16 years of age
- •Eligible to undergo auto-HSCT
- •Willing and able to follow the research procedures and conditions, with good compliance
- •Willing to receive at least the 2 years follow-up and maintain detailed medical records, including transfusion history
- •Subject and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form, and can complete all follow-ups in accordance with the protocol requirements
排除标准
- •Presence of clear contraindications for hematopoietic stem cell collection
- •Diagnosis of composite α thalassemia
- •A white blood cell (WBC) count <3×10^9/L, and/or platelet count <100×10^9/L not related to hypersplenism
- •Subjects with severe iron overload at the time of screening: severe iron overload of the liver showed by MRI, serum ferritin ≥ 5000 ng/mL, or moderate to severe iron overload of the heart
- •Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
- •Meet the criteria for allo-HSCT and with an identified willing donor with a full HLA match
- •Prior receipt of gene therapy or allo-HSCT
- •Subjects with any severe active fungal, bacterial, viral, tuberculosis or other infection, including active hepatitis B (defined as serum HBV-DNA ≥2000 IU/ml), active hepatitis C virus, HCV) infection, human immunodeficiency virus (HIV) antibody-positive or active syphilis patients, etc.
- •Immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis)
- •Diagnosis of a significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study
- •History of major organ damage including:
- •Liver function test suggest AST or ALT levels >3× upper limit of normal (ULN);
- •Total serum bilirubin value >2.5×ULN;if combined with Gilbert syndrome, total bilirubin >3×ULN and direct bilirubin value >2.5×ULN;
- •History of bridging fibrosis, cirrhosis;
- •Left ventricular ejection fraction <45%;
- •New York Heart Association (NYHA) class III or IV congestive heart failure;
- •Severe arrhythmia requiring medical treatment;
- •Uncontrolled hypertension or unstable angina pectoris;
- •Myocardial infarction or bypass or stent surgery within 12 months before drug administration;
- •Valvular disease with clinical significance;
- •Baseline calculated eGFR<60mL/min/1.73m2;
- •Pulmonary function: FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;
- •Evidence of clinically significant pulmonary hypertension requiring medical intervention.
- •Uncorrectable coagulation dysfunction or history of severe bleeding disorder
- •Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician
- •Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.)
- •Participated in other clinical studies within 3 months prior to screening
- •Inoculated live vaccine within 6 weeks prior to screening
- •Pregnancy or breastfeeding women; Subjects or their sexual partners were unable to take medically recognized effective contraceptive measures during the 27-month study period
- •The subjects or their parents would not comply with the study procedures outlined in the protocol
- •The subjects received hydroxyurea or thalidomide or hypomethylating drugs within 3 months before hematopoietic stem cell collection
- •Patients considered to be ineligible for the study by the investigator for reasons other than the above
结局指标
主要结局
The number, frequency and severity of adverse events (AE) after reinfusion of KL003 drug products
时间窗: within 6 months
The proportion of participants who meet the definition of transfusion independence (TI) for at least 6 months
时间窗: Up to 24 months post transplant
TI is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months
次要结局
未报告次要终点
研究者
研究点 (1)
Loading locations...
相似试验
进行中（未招募）
不适用
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.Transfusion-dependent Beta-ThalassemiaNCT05860595Institute of Hematology & Blood Diseases Hospital, China3
尚未招募
早期 1 期
Safety and Efficacy Study of KL002 in the Treatment of Advanced Primary PDParkinson DiseaseNCT05882487Second Affiliated Hospital, School of Medicine, Zhejiang University9
已完成
1 期
Pharmacokinetic and Safety Study of Subcutaneous and Intravenous Anifrolumab Delivered in Healthy Adult ParticipantsHealthy VolunteersNCT06662123AstraZeneca24
尚未招募
早期 1 期
Safety and Efficacy Clinical Study of Severe Hemophilia B Treatment With KL001Hemophilia B Without InhibitorNCT06125756Affiliated Hospital of Guangdong Medical University9
终止
1 期
Ethnobridging Study in Healthy Volunteers, Chinese and Japanese SubjectsChronic Hepatitis bNCT05298332Antios Therapeutics, Inc37