Overview

β-thalassemia is one of the most common inherited hemoglobinopathies worldwide and a major public health issue that severely impacts birth quality, human health, and social progress. Currently, there are limited clinical drugs specifically designed to treat patients with β-thalassemia. This clinical trial aims to evaluate the efficacy and safety of luspatercept combined with low-dose thalidomide compared with luspatercept alone in patients with thalassemia. Key questions to be answered include:

• Does luspatercept combined with low-dose thalidomide reduce the transfusion burden in patients with β-thalassemia major?
• What medical problems may occur when patients receive luspatercept combined with low-dose thalidomide? In this clinical trial, participants were randomly assigned in a 1:1 ratio to either an intervention group (luspatercept combined with low-dose thalidomide) or a control group (luspatercept combined with placebo) using a central randomization system. The clinical efficacy and safety of the two groups were evaluated. The primary outcome measure was the clinical efficacy of luspatercept combined with low-dose thalidomide in reducing the transfusion burden in patients with β-thalassemia major.

Eligibility

Inclusion Criteria:

• Age ≥ 18 years, regardless of gender;
• Patients with transfusion-dependent β-thalassemia;
• Intended treatment with rotecept combined with low-dose thalidomide or rotecept alone;
• Requires regular red blood cell transfusions (6-30 RBC units (International Units) within 24 weeks prior to randomization, with a transfusion-free interval of ≤ 42 days);
• ECOG performance status 0-1;
• Patients (or legal guardians) voluntarily participate in the study and provide signed informed consent.

Exclusion Criteria:

• A diagnosis of α-thalassemia minor, Hb Bart's edema, hemoglobin S/β-thalassemia, or myelodysplastic anemia (combination of β-thalassemia and α-thalassemia is permitted);
• Anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemia (e.g., severe G6PD deficiency, pyruvate kinase deficiency);
• A bleeding disorder manifesting as frequent bleeding (e.g., menorrhagia, epistaxis, coagulopathy);
• Hemolysis unrelated to thalassemia within the past 8 weeks, such as after use of hemolytic-inducing medications (e.g., antimalarials, nonsteroidal anti-inflammatory drugs \[NSAIDs\]);
• Use of long-term anticoagulant therapy, unless discontinued at least 28 days before randomization. Prophylactic anticoagulant therapy for surgery or high-risk procedures, as well as low-molecular-weight heparin and long-term aspirin therapy for superficial venous thrombosis, are permitted.
• Use of thalidomide alone, erythropoiesis-stimulating drugs (ESA), or hydroxyurea within the past 24 weeks.
• Use of long-term systemic glucocorticoids within the past 12 weeks.
• Use of cytotoxic drugs, immunosuppressants, or other investigational drugs within the past 28 days.
• HIV positive and/or active HCV or HBV infection.
• Hepatic and renal insufficiency (liver insufficiency, i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≥3× upper limit of normal (ULN); renal insufficiency, i.e., serum creatinine ≥3× upper limit of normal (ULN) or creatinine clearance less than 30). mL/min), history of malignancy (unless cured and/or with no known active disease);
• Women who are pregnant, plan to become pregnant during the study, or are breastfeeding;
• Previous thalassemia gene therapy or hematopoietic stem cell transplantation (HSCT);
• Platelet count \< 70 × 109/L, if not associated with hypersplenism, or platelet count \> 1,000 × 109/L;
• Other conditions deemed unsuitable for participation in this clinical trial by the investigator.