This is a non-randomized, open label, single-dose study in up to 41 participants with β-thalassemia major. The goal of this clinical trial is to evaluate the safety and efficacy of KL003 cell injection in subjects with β-thalassemia major.
This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess KL003 Cell Injection in up to 41 participants with transfusion-dependent β-thalassemia (TDT) who are ≥3 and ≤35 years of age. KL003 Cell Injection is autologous CD34+ stem cells transduced Ex Vivo with a lentiviral Vector encoding βA-T87Q-Globin.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Administered by intravenous infusion after myeloablative conditioning with busulfan.
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, China
RECRUITINGInstitute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGKL003 engraftment
Proportion of participants with successful engraftment within 42 days after KL003 infusion.
Time frame: From time of KL003 infusion through Month 2
Engraftment time of neutrophil and platelet
Neutrophil engraftment was defined as the first day when neutrophils ≥ 0.5×10\^9/L for 3 consecutive days; Platelet engraftment was defined as the first the first day of platelet count ≥ 20.0×10\^9/L for 7 consecutive days with no platelet transfusions.
Time frame: From time of KL003 infusion through Month 24
Overall Survival
Overall survival was defined as time from date of KL003 infusion to date of death.
Time frame: From time of KL003 infusion through Month 24
The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products
Frequency and severity of AEs \& SAEs identified according to NCI CTCAE 5.0
Time frame: From time of KL003 infusion through Month 24
Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation
Clonal dominance was defined as an ISA result greater than 90% of the total insertion sites (IS) at any time
Time frame: From time of KL003 infusion through Month 24
Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)
Peripheral blood samples were analyzed for detection of RCL
Time frame: From time of KL003 infusion through Month 24
The proportion of participants achieved Transfusion Independence (TI)for at least 6 months
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TI 6 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months
Time frame: From time of KL003 infusion through Month 24
The proportion of participants achieved TI 12
TI 12 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 12 months
Time frame: From time of KL003 infusion through Month 24
The start time of Transfusion Independence (TI) after KL003 infusion
The TI start time is defined as the first day of treated participants with transfusion-dependent β-thalassemia (TDT) who achieved transfusion independence.
Time frame: From time of KL003 infusion through Month 24
Total Hb and the vector-derived HbA^T87Q
The total Hb is measured by routine blood test, Therapeutic globin expression was measured by HbA\^T87Q in peripheral blood.
Time frame: From time of KL003 infusion through Month 24