NCT05860595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.
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: 2023年5月23日最近更新:
适应症
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Engraftment time of platelet
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 in subjects with transfusion-dependent β-thalassemia.
详细描述
Subject participation for this study will be 24 months. Subjects who enroll in this study will be asked to participate in a subsequent 13-year follow-up for gene therapy products.
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-up in accordance with the protocol requirements
排除标准
- •Subjects positive with the following etiological tests: human immunodeficiency virus(HIV-1-2), human cytomegalovirus (HCMV-DNA), EB virus (EBV-DNA), HBV (HBsAg/HBV-DNA positive), HCV antibody (HCV-Ab), Treponema pallidum antibody (TP-Ab)
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator
- •Contraindication to bone marrow collection
- •Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
- •A white blood cell (WBC) count <3×10^9/L, and/or platelet count <100×10^9/L not related to hypersplenism
- •Diagnosis of composite α thalassemia
- •Participants 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
- •Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody
- •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
- •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.)
- •Participation in another clinical study with an investigational drug within 30 days of Screening or participating in another clinical study with an investigational drug
- •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
- •Receipt of hydroxyurea therapy within 3 months before HSCT harvest
- •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
Engraftment time of platelet
时间窗: Up to 42 days post transplant
The first day of platelet count ≥ 20.0×10\^9/L for 7 consecutive days after platelet transfusion independence
Percentage of participants with successful lentiviral vector transduced CD34+ stem cell engraftment
时间窗: Up to 42 days post transplant
Successful engraftment was defined as neutrophil count \[ANC\] ≥0.5×10\^9/L for 3 consecutive days
Engraftment time of neutrophil
时间窗: Up to 42 days post transplant
The first day when neutrophils ≥ 0.5×10\^9/L for 3 consecutive days
Transplant-related mortality within 100 days and within 1 year after reinfusion of KL003 drug product
时间窗: Up to 1 year post transplant
The number, frequency and severity of adverse events (AE) within 1 year after reinfusion of KL003 drug products
时间窗: Up to 24 months post transplant
Frequency and severity of AEs \& SAEs identified according to NCI CTCAE 5.0
次要结局
- The proportion of participants who meet the definition of transfusion independence (TI) for at least 6 months(Up to 24 months post transplant)
- The duration of transfusion independence(Up to 24 months post transplant)
- Changes in the frequency and volume of blood transfusion(Up to 24 months post transplant)
研究者
研究点 (1)
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