Safety and Efficacy of the Lentiviral Vector in Gene Therapy of Beta-thalassemia Patients


Institute of Hematology & Blood Diseases Hospital, China




Transfusion-dependent Beta-Thalassemia


Genetic: KL003 cell injection Drug Product

Study type


Funder types




Details and patient eligibility


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 β-thalassemia major.


3 estimated patients




3 to 35 years old


No Healthy Volunteers

Inclusion criteria

  • 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

Exclusion criteria

  • 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:

    1. Liver function test suggest AST or ALT levels >3× upper limit of normal (ULN);
    2. Total serum bilirubin value >2.5×ULN;if combined with Gilbert syndrome, total bilirubin >3×ULN and direct bilirubin value >2.5×ULN;
    3. History of bridging fibrosis, cirrhosis;
    4. Left ventricular ejection fraction <45%;
    5. New York Heart Association (NYHA) class III or IV congestive heart failure;
    6. Severe arrhythmia requiring medical treatment;
    7. Uncontrolled hypertension or unstable angina pectoris;
    8. Myocardial infarction or bypass or stent surgery within 12 months before drug administration;
    9. Valvular disease with clinical significance;
    10. Baseline calculated eGFR<60mL/min/1.73m2;
    11. Pulmonary function: FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;
    12. 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

Trial design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

3 participants in 1 patient group

KL003 cell injection Drug Product
Experimental group
Traditional myeloablative conditioning regimen consists of Busulfan, which may increase the risk of irreversible pulmonary fibrosis, VOD, and infertility due to potential serious toxicity. In this study, we intend to use genetic hematopoietic stem cells (lentivirus transduction) transfusion with no conditioning regimen, which could avoid toxicity due to chemotherapy drugs.
Genetic: KL003 cell injection Drug Product

Trial contacts and locations



Central trial contact

Jun Shi, PhD; Zhen Gao, MD

Data sourced from

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