Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Study Details
Study Description
Brief Summary
This is a non-randomized, open-label, single-dose study. The aim of this study is to evaluate the safety and efficacy of the treatment with lentiviral vector encoding βA-T87Q-globin gene transduced autologous hematopoietic stem cells in subjects with β-thalassemia major.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Subject participation for this study will be 24 months. Subjects who enroll in this study will be asked to participate in a subsequent 13-year follow-up for gene therapy products.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: KL003 cell injection Drug Product Each recruited subject will accept KL003 Transplantation. |
Genetic: KL003 cell injection Drug Product
Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene.
|
Outcome Measures
Primary Outcome Measures
- Percentage of participants with successful lentiviral vector transduced CD34+ stem cell engraftment [Up to 42 days post transplant]
Successful engraftment was defined as neutrophil count [ANC] ≥0.5×10^9/L for 3 consecutive days
- Engraftment time of neutrophil [Up to 42 days post transplant]
The first day when neutrophils ≥ 0.5×10^9/L for 3 consecutive days
- Engraftment time of platelet [Up to 42 days post transplant]
The first day of platelet count ≥ 20.0×10^9/L for 7 consecutive days after platelet transfusion independence
- Transplant-related mortality within 100 days and within 1 year after reinfusion of KL003 drug product [Up to 1 year post transplant]
- The number, frequency and severity of adverse events (AE) within 1 year after reinfusion of KL003 drug products [Up to 24 months post transplant]
Frequency and severity of AEs & SAEs identified according to NCI CTCAE 5.0
Secondary Outcome Measures
- The proportion of participants who meet the definition of transfusion independence (TI) for at least 6 months [Up to 24 months post transplant]
TI is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months
- The duration of transfusion independence [Up to 24 months post transplant]
- Changes in the frequency and volume of blood transfusion [Up to 24 months post transplant]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female age between 3-35 years
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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
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Documented baseline, or pretransfusion, Hb level≤7 g/dL
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Karnofsky performance status ≥70 for subjects≥16 years of age; Lansky performance status of ≥70 for subjects<16 years of age
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Eligible to undergo auto-HSCT
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Willing and able to follow the research procedures and conditions, with good compliance
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Willing to receive at least the 2 years follow-up and maintain detailed medical records, including transfusion history
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Subject and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form, and can complete all follow-up in accordance with the protocol requirements
Exclusion Criteria:
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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), Treponema pallidum antibody (TP-Ab)
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Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator
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Contraindication to bone marrow collection
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Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
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A white blood cell (WBC) count <3×109/L, and/or platelet count <100×109/L not related to hypersplenism
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Diagnosis of composite α thalassemia
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Participants with severe iron overload at the time of screening: severe iron overload of the liver showed by MRI, serum ferritin ≥ 5000 ng/mL, or moderate to severe iron overload of the heart
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Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody
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Meet the criteria for allo-HSCT and with an identified willing donor with a full HLA match
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Prior receipt of gene therapy or allo-HSCT
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Immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis)
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Diagnosis of a significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study
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History of major organ damage including:
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Liver function test suggest AST or ALT levels >3× upper limit of normal (ULN);
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Total serum bilirubin value >2.5×ULN;if combined with Gilbert syndrome, total bilirubin >3×ULN and direct bilirubin value >2.5×ULN;
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History of bridging fibrosis, cirrhosis;
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Left ventricular ejection fraction <45%;
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New York Heart Association (NYHA) class III or IV congestive heart failure;
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Severe arrhythmia requiring medical treatment;
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Uncontrolled hypertension or unstable angina pectoris;
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Myocardial infarction or bypass or stent surgery within 12 months before drug administration;
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Valvular disease with clinical significance;
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Baseline calculated eGFR<60mL/min/1.73m2;
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Pulmonary function: FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;
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Evidence of clinically significant pulmonary hypertension requiring medical intervention.
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Uncorrectable coagulation dysfunction or history of severe bleeding disorder
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Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician
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Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.)
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Participation in another clinical study with an investigational drug within 30 days of Screening or participating in another clinical study with an investigational drug
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Inoculated live vaccine within 6 weeks prior to screening
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Pregnancy or breastfeeding women; Subjects or their sexual partners were unable to take medically recognized effective contraceptive measures during the 27-month study period
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The subjects or their parents would not comply with the study procedures outlined in the protocol
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Receipt of hydroxyurea therapy within 3 months before HSCT harvest
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Patients considered to be ineligible for the study by the investigator for reasons other than the above
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Regenerative Medicine Center | Tianjin | Tianjin | China |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
- R&D Kanglin Biotech
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CP-KL003-002/01