Transfusion-dependent ß-thalassemia
Conditions
Interventions
Group 1:Intravenous injection of autologous CD34-positive cells gene-edited in vitro by CRISPR-Cas9 gene editing system
Sponsors
the First Affiliated Hospital of Guangxi Medical University
Eligibility
Sex/Gender
All
Age
6 Years to 35 Years
Inclusion criteria
Inclusion criteria: 1. The patient voluntarily signs the informed consent form (adult or legal representative) and can complete the research procedures and follow-up inspection and treatment; 2. Aged 6~35 years, no gender limit; 3. Annual blood transfusion > 100ml/kg, or blood transfusion > 8 times per year in the first two years of enrollment; 4. Report baseline Hb concentration before blood transfusion = 60, suitable for HSCT; 6. With proper organ function, it must meet the following standards:Aspartate aminotransferase (AST) = 60 mL/min (Cockcroft and Gault formula);Possess a minimum level of lung reserve, defined as 91%;International normalized ratio (INR) <= 1.5 times ULN, and activated partial prothrombin time (aPTT) <= 1.5 times ULN; 7. Have the blood vessel conditions for mononuclear cell collection; 8. Women of childbearing age have a negative blood/urine pregnancy test within 7 days before RM-001 infusion, and any male and female patients with fertility must agree to be effective during the entire study process and at least six months after the administration of the study treatment Method of contraception. According to the judgment of the investigator, the fertility of a patient means that he/she is biologically capable of having children and having a normal sex life. Female patients who are infertile (ie, meet at least one of the following criteria):Hysterectomy or bilateral oophorectomy has been performed, or Medically confirmed ovarian failure, or Medically confirmed as postmenopausal (at least 12 consecutive months of menopause).
Exclusion criteria
Exclusion criteria: 1. Patients who tested positive for the following viruses: HIV-1/2, HTLV, HCMV, EB, COVID-19. Hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) positive, hepatitis B e antibody (HBeAb) positive, hepatitis B core antibody (HBcAb) positive, hepatitis C antibody (HCV-Ab) positive, anti-Treponema pallidum antibody (TP-Ab) Positive, those who meet one of them; 2. Platelet count = 450ms for men, >= 470ms for women (QTcB = QT/RR1/2); uncontrolled hypertension (systolic blood pressure >= 140mmHg and/or diastolic blood pressure >= 90mmHg) or pulmonary hypertension or unstable angina; before administration Myocardial infarction or bypass or stent surgery within 12 months; clinically significant valve disease; other heart diseases judged by the investigator to be unsuitable for inclusion; 5. After Hb correction or alveolar volume correction, the predicted CO diffusivity (DLco) is less than 50%; 6. MRI showed cardiac T2 > 10ms; 7. MRI shows liver T2 > 1.4ms; 8. Iron overload, serum ferritin exceeds 5000ng/ml; 9. Significant pulmonary arterial hypertension, requiring drug treatment or requiring oxygen; 10. Participate in other clinical studies within 30 days of the screening period; 11. Those who are known to have a history of hypersensitivity to the ingredients of the preparation used in the test; 12. Received live vaccine within 6 weeks before screening; 13. Have or are suffering from malignant tumor, myeloid dysplasia or immunodeficiency disease. Patients with a history of malignancy in the past and the disease has been cured for >= 5 years can be enrolled; 14. Immediate family members with or suspected of having hereditary cancer (eg, hereditary breast cancer, hereditary non-polyposis colorectal cancer); 15. Breastfeeding women; 16. Other conditions deemed inappropriate by the investigator to participate in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in the concentration of fetal hemoglobin (without blood transfusion);Reduce the proportion of blood transfusion (TR12) and get rid of blood transfusion dependence (TI12) for at least 12 months ;Peripheral blood lymphocytes;Proportion of allele changes in bone marrow cells;Quality of life assessment; | — |
Countries
China
Contacts
Public ContactLai Yongrong
The First Affiliated Hospital of Guangxi Medical University
Outcome results
None listed