A Phase I/II Clinical Study Evaluating the Safety and Efficacy of KL003 Cell Injection in Transfusion-dependent Β-thalassemia
Overview
- Phase
- Phase 1
- Intervention
- KL003 Cell Injection Drug Product
- Conditions
- Transfusion-dependent Beta-Thalassemia
- Sponsor
- Kanglin Biotechnology (Hangzhou) Co., Ltd.
- Enrollment
- 41
- Locations
- 2
- Primary Endpoint
- KL003 engraftment
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female age between 3-35 years;
- •Diagnosis of transfusion-dependent β-thalassemia and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years;
- •Karnofsky performance status ≥70 for participants≥16 years of age; Lansky performance status of ≥70 for participants\<16 years of age;
- •Eligible to undergo auto-HSCT;
- •Willing and able to follow the research procedures and conditions, with good compliance;
- •Willing to receive at least the 2 years follow-up;
- •Participant and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form.
Exclusion Criteria
- •Diagnosis of composite α thalassemia;
- •Prior receipt of gene therapy or allo-HSCT;
- •Meet the criteria for allo-HSCT and with an identified willing donor with full HLA match;
- •Participants with severe iron overload at the time of screening;
- •Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody;
- •Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.);
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator;
- •Subjects positive with the following etiological tests: human immunodeficiency virus(HIV-1-2),human cytomegalovirus (HCMV-DNA),EB virus（EBV-DNA）,HBV (HBsAg/HBV-DNA positive),HCV antibody (HCV-Ab), Human T-lymphotropic virus antibody (HTLV-Ab), Treponema pallidum antibody (TP-Ab);
- •Uncorrectable coagulation dysfunction or history of severe bleeding disorder;
- •History of major organ damage including:
Arms & Interventions
KL003 Cell Injection Drug Product
Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene
Intervention: KL003 Cell Injection Drug Product
Outcomes
Primary Outcomes
KL003 engraftment
Time Frame: From time of KL003 infusion through Month 2
Proportion of participants with successful engraftment within 42 days after KL003 infusion.
Engraftment time of neutrophil and platelet
Time Frame: From time of KL003 infusion through Month 24
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.
Overall Survival
Time Frame: From time of KL003 infusion through Month 24
Overall survival was defined as time from date of KL003 infusion to date of death.
The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products
Time Frame: From time of KL003 infusion through Month 24
Frequency and severity of AEs \& SAEs identified according to NCI CTCAE 5.0
Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation
Time Frame: From time of KL003 infusion through Month 24
Clonal dominance was defined as an ISA result greater than 90% of the total insertion sites (IS) at any time
Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)
Time Frame: From time of KL003 infusion through Month 24
Peripheral blood samples were analyzed for detection of RCL
Secondary Outcomes
- The proportion of participants achieved Transfusion Independence (TI)for at least 6 months(From time of KL003 infusion through Month 24)
- The proportion of participants achieved TI 12(From time of KL003 infusion through Month 24)
- The start time of Transfusion Independence (TI) after KL003 infusion(From time of KL003 infusion through Month 24)
- Total Hb and the vector-derived HbA^T87Q(From time of KL003 infusion through Month 24)