A Phase 1 Study of Gene-modified Autologous Hematopoietic Stem Cell (BD211) Treating β-thalassemia Major

Ki vehet részt

• Participants aged 3 years (inclusive) to 18 years (exclusive), with no gender restrictions
• Parents/legal guardians have fully understood and voluntarily signed a written informed consent form; and it is recommended that children aged 8 and above be involved in the decision to participate in this clinical trial and obtain a written consent form
• Transfusion-dependent β-thalassemia patients. "Transfusion-dependent" is defined as: requiring at least 100 mL/kg of packed red blood cells annually; the genotype can be β0/β0, β0/β+, or β+/β+, diagnosed through hemoglobin studies
• Eligible for allogeneic hematopoietic stem cell transplantation, but without a donor or those refusing to undergo allogeneic hematopoietic stem cell transplantation
• Have undergone symptomatic treatment for at least the past 2 years and have retained medical records including transfusion history
• Stable condition and maintained an appropriate iron chelation regimen
• Good status of organ function
• Good compliance from the individual and parents/legal guardians, willing to adhere to visit schedules, trial plans, laboratory tests, and other trial procedures as stipulated in this protocol
• Willing to participate in long-term follow-up research

Ki nem vehet részt

• Has a fully HLA-matched hematopoietic stem cell donor and is willing to receive a fully HLA-matched hematopoietic stem cell transplant. Enrollment is otherwise only advised after review by the safety review committee
• Received hydroxyurea treatment within the last 3 months before stem cell collection
• Used erythropoiesis-stimulating agents within the 3 months prior to HSC collection
• Previously received any type of gene and/or cell therapy
• Allergic to the investigational drug or its excipients
• Positive for antibodies against Human Immunodeficiency Virus 1/2 (HIV-1/HIV-2), Treponema pallidum (TP) specific antibodies, Human T-lymphotropic Virus 1 or 2 (HTLV-1/HTLV-2) antibodies, and Vesicular Stomatitis Virus G (VSV-G)
• Positive for Hepatitis B Virus (HBV) HbsAg or HBV-DNA; Hepatitis C Virus (HCV) HCAb positive; positive nucleic acid test for Epstein-Barr Virus (EBV) or Cytomegalovirus (CMV)
• Severe active bacterial, viral, fungal, malarial, or parasitic infections
• Has had, or currently has, a malignant, myeloproliferative, or immunodeficiency disorder
• Direct relatives with known or suspected hereditary cancer syndromes (including but not limited to breast cancer, colorectal cancer, ovarian cancer, prostate cancer, and pancreatic cancer)
• Autoimmune diseases that could result in transfusion difficulties
• Uncorrected bleeding disorders
• Severe psychiatric disorders
• History of allogeneic transplantation
• Any other conditions determined by the investigator as unsuitable for participation in this clinical trial
• Major organ diseases or abnormal lab tests, including:; Liver cirrhosis, fibrosis, or active hepatitis, and/or abnormal liver function tests (Serum total bilirubin (TBIL) ≥ 1.5x Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≥ 2.5x ULN; Alkaline phosphatase ≥ 2.5x ULN); Heart disease, or Left Ventricular Ejection Fraction (LVEF) < 60%; Kidney diseases, or serum creatinine ≥ 1.5ULN, creatinine clearance rate < 30% of the normal level (measured or calculated by the Cockcroft-Gault equation); Endocrine disorders, such as insulin-dependent diabetes, hyperthyroidism, or hypothyroidism; Severe iron overload, serum ferritin ≥ 5000 ng/mL; Cardiac T2* < 20 ms, and/or liver iron content (LIC) ≥ 15mg/g liver weight by MRI; Significant pulmonary hypertension diagnosed clinically according to guidelines, requiring clinical medical intervention
• Peripheral blood white cell (WBC) count < 3x10\^9/L or platelets count < 120x10\^9/L
• Participating in another clinical trial and is within a 30-day screening period
• Has contraindications to anesthesia
• Has contraindications to hematopoietic stem cell collection