thalassemia major
Conditions
Interventions
Experimental group:KL003 cell injection transfusion
Sponsors
Affiliated Hospital of Guangdong Medical University
Eligibility
Sex/Gender
All
Age
3 Years to 35 Years
Inclusion criteria
Inclusion criteria: (1)Participants between 3 and 35 years of age, inclusive, at the time of screening; (2)Diagnosis of transfusion-dependentß-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or =8 transfusions of pRBCs per year for the prior 2 years; (3) Subjects must be stable and maintained on an appropriate iron chelation regimen; (4)Documented baseline, or pretransfusion, Hb level=7 g/dL; (5)Have a Karnofsky performance status of =70 for subjects=16 years of age(inclusive),and a Lansky performance status of =70 for subjects<16 years of age; (6)Eligible to undergo HSCT,but cannot carry out allogeneic hematopoietic stem cell transplantation for various reasons; (7)Willing and able to follow the research procedures and conditions, with good compliance; (8)Willing to receive at least the 2 years follow-up and maintained detailed medical records, including transfusion history; (9)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
Exclusion criteria
Exclusion criteria: (1)Subjects positive with the following etiological tests:human immunodeficiency virus(HIV-1-2),human cytomegalovirus (HCMV-DNA),EB virus(EBV-DNA)COVID-19(Nasal and/or pharyngeal swabs undergo re-screening after the nucleic acid assay turns negative),HBV (HBsAg/HBV-DNA positive),HCV antibody (HCV-Ab),Treponema pallidum (anti-Treponema pallidum antibody)and syphilis rapid serologic reaction positive; (2)Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator; (3)Contraindication to bone marrow collection; (4)Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder; (5)A white blood cell (WBC) count 3× upper limit of normal(ULN); b.Total serum bilirubin value>2.5×ULN;if combined with Gilbert syndrome, total bilirubin>3×ULN and direct bilirubin value>2.5×ULN; c.History of bridging fibrosis, cirrhosis; d.Left ventricular ejection fraction <45%; e.New York Heart Association (NYHA) class III or IV congestive heart failure; f.Severe arrhythmia requiring medical treatment; g.Uncontrolled hypertension or unstable angina pectoris; h.Myocardial infarction or bypass or stent surgery within 12 months before drug administration; i.Valvular disease with clinical significance; j.Baseline calculated eGFR<60mL/min/1.73m2; k.Pulmonary function:FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction; l.Evidence of clinically significant pulmonary hypertension requiring medical intervention. (10)Uncorrectable coagulation dysfunction or history of severe bleeding disorder; (11)Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician; (12)Known allergy to clinical trial drug or ingredient; (13)Participation in another clinical study with an investigational drug within 30 days of Screening or is Participating in another clinical study with an investigational drug; (14)Inoculated live vaccine within 6 weeks prior screening (15)Pregnancy or breastfeeding women;Subjects or their sexual partners were unable to take medically recognized effective contraceptive measures during the 27-month study period; (16)The subjects or their parents would not comply with the study procedures outlined in the protocol; (17)Receipt of Hydroxyurea therapy within 3 months before HSCT harvest; (18)Any other condition that not suitable to participate in this clinical trial as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| engraftment time of Neutrophil and Platelet;Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs);Overall survival;Percentage of Participants With Vector-Derived Replication-Competent Lentivirus; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Treated Participants With Transfusion-Dependent ß-Thalassemia (TDT) Who Achieved Transfusion Independence (TI);Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent ß-Thalassemia (TDT);Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume and Number; | — |
Countries
China
Contacts
Public ContactHuang Jinqi
Affiliated Hospital of Guangdong Medical University
Outcome results
None listed