Luspatercept plus low-dose thalidomide for adults with transfusion-dependent β-thalassemia

Evaluation of the Clinical Efficacy and Safety of Luspatercept Combined With Low-dose Thalidomide Versus Luspatercept Alone in the Treatment of Adult Patients With Transfusion-dependent β-thalassemia

This study tests whether adding low-dose thalidomide to luspatercept helps adults with transfusion-dependent β-thalassemia need fewer red blood cell transfusions.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Guangxi Medical University (Academic / other)
• Locations: 8 sites (Shenzhen, Guangdong and 7 other locations)
• Trial ID: NCT07338344 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial enrolling adults with transfusion-dependent β-thalassemia. Participants are centrally randomized 1:1 to receive luspatercept plus low-dose thalidomide or luspatercept plus placebo through a screening/run-in period, a 24-week double-blind treatment period and a follow-up period. The primary endpoint is the proportion of subjects who reduce RBC transfusion burden by ≥50% and at least 2 units during weeks 13–24 versus their 12-week baseline. Secondary outcomes include other efficacy measures, iron metabolism, hemolysis markers, safety, and adverse event rates.

Who should consider this trial

Good fit: Adults (age ≥18) with transfusion-dependent β-thalassemia who require regular red blood cell transfusions (6–30 units in the prior 24 weeks with transfusion-free intervals ≤42 days) and have ECOG 0–1 are the intended participants.

Not a fit: People whose anemia is due to non–β-thalassemia causes, those with contraindications to thalidomide (including pregnant people or those of childbearing potential without strict contraception), or with other excluded hematologic disorders are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could substantially reduce transfusion needs and related iron overload for adults with transfusion-dependent β-thalassemia.

How similar studies have performed: Luspatercept alone has demonstrated reduced transfusion burden in prior large trials, while combining luspatercept with thalidomide is a more novel approach with limited prior data.

Eligibility criteria

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.

Where this trial is running

Shenzhen, Guangdong and 7 other locations

• Southern Medical University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)
• Affiliated Hospital of Youjiang Medical College for Nationalities — Baise City, Guangxi, China (Recruiting)
• Baise People's Hospital — Baise City, Guangxi, China (Recruiting)
• Liuzhou People's Hospital — Liuzhou, Guangxi, China (Recruiting)
• Liuzhou Workers' Hospital — Liuzhou, Guangxi, China (Recruiting)
• Yulin First People's Hospital — Yulin, Guangxi, China (Recruiting)
• Yunnan Provincial First People's Hospital — Kunming, Yunnan, China (Recruiting)
• The First Affiliated Hospital of Guangxi Medical University — Naning, China (Recruiting)

Study contacts

• Study coordinator: Rongrong Liu

Conditions Transfusion-dependent β-thalassemia Patients