Evaluating the Clinical Efficacy and Safety of Luspatercept Combined With Thalidomide in the Treatment of β-TDT Patients

NCT07338344 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-K0444
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Transfusion-dependent β-thalassemia Patients

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Erythroid Response - Week 13 to Week 24

  Percentage of participants with a ≥50% reduction in RBC transfusion burden compared to baseline (RBC transfusion burden during the 12 weeks before randomization) and a reduction of at least 2 units for 12 consecutive weeks between Weeks 13 and 24 after randomization

  Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24

Secondary Outcomes (15)

• Percentage of Participants Who Achieved ≥ 50% And a Reduction of ≥ 2 RBC units From Baseline in Transfusion Burden- Week 37 to Week 48

  Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48

• Percentage Of Participants Who Achieved ≥ 33% And a Reduction of ≥ 2 RBC units Reduction From Baseline in Transfusion Burden - Week 37 to Week 48

  Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48

• Percentage Of Participants Who Achieved ≥ 50% Reduction From Baseline in Transfusion Burden - weeks 1-12, 13-24, 25-36, 37-48

  Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48

• Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - weeks 1-12, 13-24, 25-36, 37-48

  Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48

• Percentage Of Participants Who Achieved ≥ 50% Reduction From Baseline in Transfusion Burden - weeks 1-24, 25-48

  Baseline: Day -83 to Day 1; Treatment: Weeks1-24, 25-48

Other Outcomes (4)

• Percent Change From Baseline to End of Treatment in Fetal hemoglobin

  Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)

• Change From Baseline to End of Treatment in γ-Globin Gene

  Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)

• Concentration Change From Baseline to End of Treatment in Hemolysis Indices

  Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)

Study Arms (2)

Luspatercept(Reblozyl) combined with low-dose thalidomide

EXPERIMENTAL

The subjects in the intervention group were treated with Luspatercept (starting dose 1.0 mg/kg, once every 21 days) combined with low-dose thalidomide (starting dose level 50 mg/d) for 48 weeks.

Drug: Luspatercept combined with low-dose thalidomide

Luspatercept plus placebo

PLACEBO COMPARATOR

The control group was treated with Luspatercept (starting dose level 1.0 mg/kg every 21 days) plus placebo (starting dose level 50 mg/d) for 48 weeks.

Drug: Luspatercept plus placebo

Interventions

Luspatercept plus placebo DRUG

The control group was treated with Luspatercept (starting dose level 1.0 mg/kg every 21 days) plus placebo (starting dose level 50 mg/d) for 48 weeks.

Luspatercept plus placebo

Luspatercept combined with low-dose thalidomide DRUG

The intervention group was treated with Luspatercept (starting dose level 1.0 mg/kg, once every 21 days) combined with low-dose thalidomide (starting dose level 50 mg/d) for 48 weeks.

Luspatercept(Reblozyl) combined with low-dose thalidomide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rongrong Liu: lead

Study Sites (8)

Southern Medical University Shenzhen Hospital

Shenzhen, Guangdong, 518100, China

RECRUITING

Affiliated Hospital of Youjiang Medical College for Nationalities

Baise City, Guangxi, 533000, China

RECRUITING

Baise People's Hospital

Baise City, Guangxi, 533000, China

RECRUITING

Liuzhou People's Hospital

Liuchow, Guangxi, 545007, China

RECRUITING

Liuzhou Workers' Hospital

Liuchow, Guangxi, 545007, China

RECRUITING

Yulin First People's Hospital

Yulin, Guangxi, 537000, China

RECRUITING

Yunnan Provincial First People's Hospital

Kunming, Yunnan, 650100, China

RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Naning, 530000, China

RECRUITING

MeSH Terms

Interventions

Thalidomide; luspatercept

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Rongrong Liu

CONTACT

+86 0771 5356510; liurongrong@stu.gxmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This trial was conducted using a double-blind approach, meaning that neither the researchers nor the subjects knew the group assignments or the interventions they were receiving. Furthermore, the outcome assessors were also blinded, objectively evaluating the outcome measures without knowing the groups assigned to the subjects.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: consultant; professor

Study Record Dates

• First Submitted: December 6, 2025
• First Posted: January 13, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)