Safety and Efficacy of the Lentiviral Vector in Gene Therapy of Beta-thalassemia Patients

NCT06219239 | Recruiting DMC

• 1 other identifier: IIT2023084
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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 transfusion in subjects with transfusion-dependent β-thalassemia.

Conditions

Transfusion-dependent Beta-Thalassemia

Keywords

Beta-Thalassemia; Hematopoietic Stem-Cell Transplantation; KL003; Gene therapy; no conditioning regimen

Outcome Measures

Primary Outcomes (2)

• The number, frequency and severity of adverse events (AE) after reinfusion of KL003 drug products

  within 6 months

• The proportion of participants who meet the definition of transfusion independence (TI) for at least 6 months

  TI is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months

  Up to 24 months post transplant

Study Arms (1)

KL003 cell injection Drug Product

EXPERIMENTAL

Traditional myeloablative conditioning regimen consists of Busulfan, which may increase the risk of irreversible pulmonary fibrosis, VOD, and infertility due to potential serious toxicity. In this study, we intend to use genetic hematopoietic stem cells (lentivirus transduction) transfusion with no conditioning regimen, which could avoid toxicity due to chemotherapy drugs.

Genetic: KL003 cell injection Drug Product

Interventions

KL003 cell injection Drug Product GENETIC

No conditioning regimen for transfusion of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene

KL003 cell injection Drug Product

Eligibility Criteria

• Age: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Documented baseline, or pretransfusion, Hb level≤7 g/dL
• Karnofsky performance status ≥70 for subjects≥16 years of age; Lansky performance status of ≥70 for subjects\<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 and maintain detailed medical records, including transfusion history
• Subject and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form, and can complete all follow-ups in accordance with the protocol requirements

You may not qualify if:

• Presence of clear contraindications for hematopoietic stem cell collection
• Diagnosis of composite α thalassemia
• A white blood cell (WBC) count \<3×10\^9/L, and/or platelet count \<100×10\^9/L not related to hypersplenism
• Subjects 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
• Any prior or current malignancy or myeloproliferative or significant immunodeficiency disorder
• Meet the criteria for allo-HSCT and with an identified willing donor with a full HLA match
• Prior receipt of gene therapy or allo-HSCT
• Subjects with any severe active fungal, bacterial, viral, tuberculosis or other infection, including active hepatitis B (defined as serum HBV-DNA ≥2000 IU/ml), active hepatitis C virus, HCV) infection, human immunodeficiency virus (HIV) antibody-positive or active syphilis patients, etc.
• 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)
• Diagnosis of a significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study
• History of major organ damage including:
• Liver function test suggest AST or ALT levels \>3× upper limit of normal (ULN);
• Total serum bilirubin value \>2.5×ULN;if combined with Gilbert syndrome, total bilirubin \>3×ULN and direct bilirubin value \>2.5×ULN;
• History of bridging fibrosis, cirrhosis;
• Left ventricular ejection fraction \<45%;

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Kanglin Biotech: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Jun Shi, PhD

CONTACT

13752253515; shijun@ihcams.ac.cn

Zhen Gao, MD

CONTACT

gaozhen@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: January 23, 2024
• Study Start: January 4, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-03

Locations

CN (1)