This study will be intented to evaluate the safety, tolerability, and engraftment efficacy after myeloablative preconditioning and transplantation of autologous CD34+ hematopoietic stem cells transduced with a lentiviral vector encoding the human βA-T87Q-globin gene in patients with transfusion-dependent (TDT) β-thalassemia.
This is an open-label, single-dose study of BD211 in patients with transfusion-dependent β-thalassemia aged 3 to 18 years. It is estimated that 10 subjects will be enrolled. BD211 is a gene modified gene therapy product designed to produce healthy β-globin in red blood cells in beta-thalassemia patients. The total follow-up duration was 24 months, the safe endpoints and effectiveness endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent β-thalassemia.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Genetically modified CD34+ autologous stem cells were transfused intravenously with single dosing.
Shanghai Children's Medical Centre
Shanghai, China
RECRUITINGPercentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence (TI) for at least 6 months
TI defined as peripheral blood weighted average hemoglobin (Hb) \> or = 9 g/dL without packed red blood cell (pRBC) transfusion for 60 days after BD211 treatment, and transfusion is continuously halted for 12 months.
Time frame: 24 months
Hb (g/dL) level between 12 and 24 months after BD211 treatment compared with baseline Hb level
Hb (g/dL) in 12, 15, 18, 21 and 24 months after drug product infusion are tested and calculated.
Time frame: 24 months
Parameters of efficacy related to TI achievement after BD211 treatment
including a. Duration to achieve TI; b. Time from BD211 infusion to last transfusion; c. Time to reach TI from BD211 infusion; d. Mean weighted Hb (g/dL) during TI; and e. Proportion of patients achieving TI at 24 month after BD211 treatment.
Time frame: 24 months
Parameters of efficacy related to reduced blood transfusion after BD211 treatment
Including a. Using the transfusion volume from the 2 years prior to the participant's enrollment as a baseline, compared with the transfusion volume between 12 and 24 months after BD211 treatment (mL/kg/month, mL/kg/year), the proportion of participants categorized based on a reduction in transfusion volume of 50%, 75%, 90%, and 100%; b. Using the number of transfusions from the 2 years prior to the participant's enrollment as a baseline, comparing the changes in the volume of pRBC transfusions at 12 and 24 months after BD211 treatment; c. Using the transfusion requirement volume from the 2 years prior to the participant's enrollment as a baseline, comparing the changes in the pRBC transfusion requirement volume at 12 and 24 months after BD211 treatment.
Time frame: 24 months
Parameters of iron overload after BD211 treatment
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Including a. Time from the last iron-chelation treatment to the last follow-up within 24 months; b. Decrease in serum ferritin level compared from baseline to 6 months and 12 months after BD211 infusion; c. Number and proportion of participants who did not require iron-chelation treatment for at least 6 months after BD211 infusion; d. Comparison of cardiac MRI T2 values at the end of the 24 month after BD211 treatment with the baseline values.
Time frame: 24 months
Parameters of growth and development after BD211 treatment
Percentage of pediatric participants reaching the standard for bone age, height, and weight at the same age, at baseline and 24 months after BD211 treatment.
Time frame: 24 months
Change in quality of life from baseline
Comparison of Pediatric Quality of Life Inventory (PedQL) scores in pediatric participants at 24 months after BD211 treatment with the scores at baseline.
Time frame: 24 months
Total hospitalizing days at 12, and 24 months (discharge after transplant)
Total hospitalizing days at 12, and 24 months after transplantation were counted.
Time frame: 24 months
Measurement of PD/PK parameters
Including a. The number and percentage of participants, in whom the HbAT87Q containing the βT87Q-globin remains at or above ≥2.0 g/dL for 6 months or longer, at 18 and 24 months after BD211 infusion; b. Average vector copy number (VCN) of the BD211 lentiviral vector in peripheral blood and bone marrow cells within 24 months after BD211 product infusion; c. Dose-response relationship within 24 months after BD211 infusion.
Time frame: 24 months
Neutrophil engraftment and platelet engraftment
Neutrophil engraftment was defined as the first of absolute neutrophil count (ANC) \> or = 0.5 ×10\^9/ L for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value less than (\<) 0.5 × 10\^9/L. Platelet engraftment was defined as the first of 3 consecutive platelet values \> or =20 × 10\^9/L for participants on different days with no platelet transfusionsadministered for 7 days immediately preceding. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Time frame: 24 months
Transplant-related mortality in 3 months and 12 months
Transplant related mortality was definedas any death occurring in the study post drug product infusion deemed related to the transplant bythe investigator.
Time frame: 12 months
Overall survival
Overall survival was defined as time from date of BD211 Drug Product infusion (Day 1) to date of death. Overall survival was censored at the date of last visit if the participant was still alive.
Time frame: 24 months
RCL incidence
Subjects blood RCL was detected with specific assay method, and the incidence was calculated at different scheduled timeslots.
Time frame: 24 months
Characterized insertion mutagenesis events that lead to clonal dominance or leukemia
The number of insertion mutagenesis events that characterized clonal dominance or leukemia was collected.
Time frame: 24 months
Frequency and severity of AE
An AE was any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE may include a change in physical signs, symptoms, and/or clinically significant laboratory change occurring in any phase of a clinical study.
Time frame: 24 months