a study evaluating the safety and efficacy of lentired drug product in transfusion-dependent β-thalassemia [tdt]

Conditions: Transfusion Dependent Beta-Thalassemia

Summary: this is a single-arm, open label, single-dose study in subjects with transfusion dependent β-thalassaemia. the study will evaluate the safety and efficacy of autologous cd34+ human hematopoietic stem cells that was transduced with lentired lentivrial vector.

subject participation for this study will be 5 years.

Eligibility criteria:
inclusion criteria: 1. the subject himself/herself or one legal guardian/agent of the subject is required to fully understand the study and voluntarily sign a written informed consent. 2. ages 5 to 35, no gender limitation. 3. the clinical diagnosis of tdt includes β0/β0, β+/β0, βe/β0 and β+/β+ genotypes. tdt was defined as severe anemia in patients with thalassemia (hb persistent \<70 g/l), regular rbc transfusion and standard iron removal therapy to survive for life. 4. karnofsky level of performance (kps) score ≥70 in adult subjects and lansky level of performance (lps) score ≥70 in children subjects. 5. subjects were determined to undergo autologous hematopoietic stem cell transplantation by the principle investigator. 6. subjects must have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history. exclusion criteria: 1. hepatitis b virus (hbv) : hbsag or hbcab positive, nucleic acid test positive; hepatitis c virus (hcv) : hcab positive, nucleic acid test positive; positive for human immunodeficiency virus (hiv) antibody or treponema pallidum (tp) specific antibody; tuberculosis: positive interferon gamma release test. 2. a white blood cell (wbc) count \<3×10\^9/l and/or platelet count \<100×10\^9/l, splenectomy was performed before. 3. uncured bleeding abnormalities. 4. any previous or current malignancy, myeloproliferative disease, or immune deficiency disease. 5. immediate family member with a known or suspected familial cancer syndrome (including but not limited to hereditary breast and ovarian cancer syndromes, hereditary non-polyposis colorectal cancer syndromes and familial adenomatous polyposis). 6. previous hematopoietic stem cell transplantation (hsct). 7. advanced liver disease, defined as: 1) baseline alanine aminotransferase (alt) or direct bilirubin ≥3 normal upper limit (uln), or 2) liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or acute hepatitis. 8. baseline estimated glomerular filtration rate (egfr) \< 70 ml/min /1.73 m2, as determined using the chronic kidney disease epidemiology collaboration (ckd-epi) creatinine equation for ≥18 years of age, and besides schwartz equation calculator \< 18 years of age. 9. uncontrolled seizure disorder. 10. diffusion capacity of carbon monoxide dispersion (dlco) \<50% of predicted (corrected for hemoglobin and or alveolar ventilation, as clinically indicated ). 11. a cardiac t2\* \<20 ms by magnetic resonance imaging (mri). 12. severe iron overload, which in the opinion of the physician is grounds for exclusion. 13. clinically significant pulmonary hypertension. 14. participation in another clinical study with an investigational drug within 30 days of screening. 15. failure to obtain appropriate informed consent. 16. any other condition that would render the subject ineligible for hsct, as determined by the attending transplant physician or investigator. 17. contraindications to the conditioning regimen. 18. prior receipt of genetic stem cell therapy. 19. diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study. 20. pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. females of child-bearing potential are required to use effective contraception from the screening period until at least 6 months after drug product infusion. male subjects are also required to use effective contraception (including condoms) from the screening period until at least 6 months after drug product infusion. 21. live vaccines were administered within 6 weeks prior to screening. 22. known history of hypersensitivity to the ingredients used in the trial. 23. an assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol.

Keywords: lentired beta-thalassemia human hematopoietic stem cell gene therapy cd34+