Gene Therapy for Beta-Thalassemia Major Using Autologous Hematopoietic Stem Cell Genetically Modified

This is an interventional treatment trial for Beta Thalassemia Major focused on measuring Beta thalassemia, Gene therapy, Beta-globin, Hematopoietic stem cells, Lentiviral vector Read More

Inclusion Criteria:

• Subjects must be 8 years of age or older.
• Subjects or their parents/legal guardians must be able to understand and voluntarily sign an informed consent form.

• Subjects must have a confirmed diagnosis of ß-thalassemia major and

  ≥100 mL/kg/year of pRBCs or ≥ 8 transfusions of pRBCs per year over a minimum of two years prior to entry onto the study.

• Subjects must be in clinically stable condition and eligible for hematopoietic stem cell transplantation.

• Subjects must satisfy Karnofsky index ≥80% for adults or Lansky index

  ≥70% for children.

• Subjects must have survival expectancy of greater than 6 months.
• Subjects must have been treated and followed up for at least the past 2 years in specialized institutions where they have comprehensive assessment of the disease（including psychiatric assessment），and detailed medical materials at least the past 2years so as to self-contrast before and after treatment.
• Subjects must discontinue treatment of hydroxyurea, 5-azoside or cytarabine at least three months prior to entry onto the study.

Exclusion Criteria:

• Having an HLA-matched donor(sibling or of a suitable 10/10 matched unrelated donor).
• Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment).
• Contraindication to anesthesia for bone marrow collection.
• Severe, bacterial, active viral, or fungal infection, etc.
• The history of malignant tumor.
• The white blood cell (WBC) count <3000/uL and/or platelet count <100,000/uL exclude hypersplenism factor.
• Family history of familial cancer syndromes (including but not limited to Hereditary breast and ovarian syndrome, hereditary non-polyp colorectal cancer syndrome, familial adenomatous polyposis).
• Previous allogeneic bone marrow transplantation.
• The history of psychosis and any psychiatric disorder.
• Active substance abuse, drug or alcohol abuse recently.
• The history of complex allo-immunization which could cause difficulty administering transfusions.
• Female adults who are pregnant , breast feeding or lack of effective contraception.
• History of major organ damage including:

Severe cerebrovascular disease or cognitive sequelae, including hemiplegia. Severe liver disease with alanine transaminase (ALT) >3 upper limit of normal. Severe liver cirrhosis or fibrosis on liver biopsy. Heart disease with ejection fraction<25% or T2* <10 ms by magnetic resonance imaging (MRI). Kidney disease with creatinine clearance <30% normal value. Lung disease, including pulmonary fibrosis, pulmonary arterial hypertension or pulmonary function tests below standard (i.e., pO2<90 mmHg and/or carbon dioxide diffusion coefficient<50%). Endocrine disorder including insulin dependent diabetes mellitus, Hyperthyroidism or deficiency, Hyperparathyroidism or deficiency.

• Participation in another clinical study within 30 days of screening.
• Subjects with severe iron overload determined by the researchers.
• Any other situation that unsuitably undergoing hematopoietic stem cell transplantation determined by the physicians or researchers.
• Presence of chromosomal abnormalities by bone marrow detected.