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Safety and Efficacy of Gene Modified Autologous Hematopoietic Stem Cells to Treat Transfusion-dependent Beta-thalassemia
Bu çalışma, transfüzyona bağımlı beta-talasemi (transfusion-dependent beta-thalassemia) hastalarında BD211 tedavisini değerlendiriyor. Yöntemde hastanın kendi CD34+ hematopoetik kök hücreleri, insan βA-T87Q-globin genini taşıyan lentiviral vektörle değiştiriliyor ve miyeloablatif hazırlık tedavisinin ardından hastaya geri veriliyor; güvenlilik, tolere edilebilirlik ve hücrelerin tutunma (engraftman) başarısı ölçülüyor. Çalışmaya 3-18 yaş arası hastalar alınıyor ve ebeveyn/yasal vasi onamı gerekiyor.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria:
1. Ages 3 to 18 years old, including:
The parents or legal guardians must be able to understand and provide ICFs. If available, it is strongly recommended that children aged ≥8 years in treatment decisions and obtain written ICFs and be clearly documented; Diagnosed as Transfusion Dependent β-thalassemia with any genotype (β0, β+, βE/β0, βS/S, βS/β0, βS/β+), confirmed the Hb analysis. No alfa chain genetic abnormalities. Subjects must stabilize and maintain an appropriate iron chelation regimen. Transfusion-dependent types are defined as requiring at least 100 mL/kg/ year of red blood cells (pRBCs).
2. No eligiblity for allogeneic hematopoietic stem cell transplantation.
3. The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
4. The subjects' parents/legal guardians must be willing and able to follow the study procedures in the study protocol.
5. Good organs' functions.
6. Having complete medical records including a history of blood transfusions testified subject received treatment and followed up for at least two years prior to screening .
Exclusion Criteria:
1. Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
2. HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
3. An active bacterial, viral, fungal or parasitic infection.
4. Contraindicated for the extraction of bone marrow under anesthesia.
5. Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
6. Peripheral blood white blood cell (WBC) count \< 3×10\^9/L or platelet count \< 120×10\^9/L.
7. A history of allo-transplantation.
8. Erythropoietin was used within 3 months prior to HSC cell collection.
9. Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
10. Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
11. Active recurrent malaria.
12. Had autoimmune diseases that may make blood transfusions difficult.
13. History of major organ injury including:
Liver disease, transaminase \> 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction \< 25%; Kidney disease, creatinine clearance \< 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 \* \< 10 ms; Significant pulmonary hypertension needing clinical medical intervention.
14. There are bleeding diseases that have not been cured.
15. The subject involved with another clinical study in a 30-day screening period.
16. Allergic to the research drug and its excipients.
17. Prior treatment with any type of gene and/or cell therapy.
18. As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
19. Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
20. Had diseases that interfere with hematopoietic stem cells collections.
21. Any other conditions being ineligible for HSC transplantation determined by the investigator.