Transfusion dependent ß-thalassemia
Conditions
Interventions
Intervention group:KL003 cell injection solution
Sponsors
Guabgzhou First People‘s Hospital
Eligibility
Sex/Gender
All
Age
8 Years to 35 Years
Inclusion criteria
Inclusion criteria: 1. At the time of screening, the age of the subjects was 8-35 years old (including the boundary value), and the gender was not limited; 2. Diagnosed with transfusion-dependent ?-thalassemia, and at least 100 mL/kg of red blood cells per year or >=8 times of red blood cell transfusion per year within two years prior to screening; 3. KPS (Karnofsky level of performance) score (subjects aged 16 years and above) score or LPS (Lansky level of performance) score (subjects under 16 years old) score >= 70 points; 4. Have the conditions for autologous hematopoietic stem cell transplantation; 5. Willing and able to comply with study procedures and conditions with good compliance; 6. Willing to undergo treatment and follow-up for at least two years, with detailed medical records, including blood transfusion history; 7. The person and/or his/her guardian voluntarily participated in this clinical trial and signed the informed consent form, and was able to complete all the follow-up contents according to the requirements of the protocol.
Exclusion criteria
Exclusion criteria: 1. Patients with positive test for the following pathogens: HIV (HIV-1/2), human cytomegalovirus (HCMV-DNA), EPSTEIN-B virus (EBV-DNA), hepatitis B (hepatitis B surface antigen (HBsAg) or hepatitis B virus DNA (HBV-DNA) positive), hepatitis C antibody (HCV-Ab), Treponema pallidum antibody (TP-Ab); 2. Clinically significant active bacterial, viral, fungal or parasitic infection as judged by the investigator at the time of screening; 3. Those with clear contraindications to stem cell collection; 4. Any previous or present malignant tumor or myeloproliferative or immunodeficiency disease; 5. White blood cell count =5000 ng/ml or cardiac moderate to severe iron overload; 8. Positive for irregular antibodies or platelet antibodies; 9. Willing donors who meet the conditions for allogeneic hematopoietic stem cell transplantation and have found HLA-compatible donors; 10. Those who have received gene therapy or allogeneic transplantation; 11. Immediate family members with known or suspected familial cancer syndromes (including but not limited to hereditary breast cancer and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, familial adenomatous polyposis, etc.); 12. Diagnosed with a major mental illness or a tendency to mental illness, which will seriously affect the ability to participate in clinical research; 13. Have a history of major organ injury, including: (1) Liver function tests show AST or ALT > 3 × ULN; (2) Total serum bilirubin > 2.5 × ULN; In Gilbert syndrome, total bilirubin > 3 × ULN and direct bilirubin > 2.5 × ULN; (3) History of bridging liver fibrosis and liver cirrhosis, and active hepatitis; (4) Left ventricular ejection fraction (LVEF) <45%; (5) New York Heart Association (NYHA) Class III or IV congestive heart failure (see Appendix 1 for NYHA heart failure classification); (6) severe arrhythmias requiring treatment; (7) Uncontrolled hypertension or unstable angina; (8) Myocardial infarction or bypass or stent surgery within 12 months prior to administration; (9) Clinically significant valvular disease; (10) Calculated eGFR<60mL/min/1.73m^2; (11) Pulmonary function: FEV1/FVC <60% and/or diffusion function accounted for less than 60% of the predicted value; (12) Evidence of pulmonary hypertension that is clinically evident requiring medical intervention; 14. History of uncorrectable coagulation dysfunction or severe bleeding disorder; 15. Any other condition that, in the opinion of the doctor, makes the subject unsuitable for hematopoietic stem cell transplantation; 16. Those who are known to be allergic to the test drug (plerixafor or G-CSF, etc.) or components (DMSO, etc.); 17. Participated in or is participating in other interventional clinical studies within 3 months prior to screening; 18. Have received a live vaccine within 6 weeks before screening; 19. Pregnant or lactating women; Subject or his/her sexual partner is unable to use medically recognized effective contraception during the 27-month study period; 20. Subjects or their parents do not have good compliance with the study protocol; 21. Received hydroxyurea therapy within 3 months prior to hematopoietic stem cell collection; 22. Any other condition that, in the opinion of the investigator, is not suitable to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs);Engraftment time of Neutrophil and Platelet;Proportion of subjects with vector-derived RCL;Cloning predominance or secondary tumors caused by mutations in the insertion site of lentiviral vectors; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving tranfusion-indepent for 6 months;Duration of tranfusion-indepent; | — |
Countries
China
Contacts
Public ContactShunqing Wang
The First People's Hospital of Guangzhou
Outcome results
None listed