Evaluating the Clinical Efficacy and Safety of Luspatercept Combined With Thalidomide in the Treatment of β-TDT Patients
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorRongrong Liu
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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);
Disqualifiers
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]);
Trial design
Design model
Parallel
Treatments tested in this trial
Luspatercept combined with low-dose thalidomide
DrugThe 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 plus placebo
DrugThe 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.
Treatment groups
78 Participants
are divided into 2 treatment groupsGroup A: Luspatercept(Reblozyl) combined with low-dose thalidomideExperimental treatment 1 intervention
Group B: Luspatercept plus placeboPlacebo comparator 1 intervention
Trial outcomes
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
Time frame
Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24Secondary outcomes
1
Percentage of Participants Who Achieved ≥ 50% And a Reduction of ≥ 2 RBC units From Baseline in Transfusion Burden- Week 37 to Week 48
Percentage of participants who achieved a ≥50% reduction in RBC transfusion burden relative to baseline, with a reduction of ≥ 2 RBC units, for 12 consecutive weeks between 37 and 48 weeks after randomization.
Time frame
Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 482
Percentage Of Participants Who Achieved ≥ 33% And a Reduction of ≥ 2 RBC units Reduction From Baseline in Transfusion Burden - Week 37 to Week 48
Percentage Of participants who achieved a ≥33% reduction in RBC transfusion burden relative to baseline, with a reduction of ≥ 2 RBC units, for 12 consecutive weeks between 37 and 48 weeks after randomization.
Time frame
Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 483
Percentage Of Participants Who Achieved ≥ 50% Reduction From Baseline in Transfusion Burden - weeks 1-12, 13-24, 25-36, 37-48
Percentage Of participants who achieved a ≥50% reduction in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) for any consecutive 12 weeks (weeks 1-12, 13-24, 25-36, 37-48).
Time frame
Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-484
Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - weeks 1-12, 13-24, 25-36, 37-48
Percentage Of participants who achieved a ≥33% reduction in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) for any consecutive 12 weeks (weeks 1-12, 13-24, 25-36, 37-48).
Time frame
Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48Other outcomes
1
Percent Change From Baseline to End of Treatment in Fetal hemoglobin
Percent changes from baseline in fetal hemoglobin (HbF) at weeks 12, 24, 36, and 48 after randomization
Time frame
Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)2
Change From Baseline to End of Treatment in γ-Globin Gene
Change from baseline to end of treatment in γ-globin geneγ-globin gene expression at weeks 12, 24, 36, and 48 after randomizatio
Time frame
Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)3
Concentration Change From Baseline to End of Treatment in Hemolysis Indices
Changes in concentration values from baseline to end of treatment in hemolysis indices the changes in hemolysis indicators (total bilirubin (TIBL), indirect bilirubin (IBIL), lactate dehydrogenase (LDH), and reticulocytes) relative to baseline at weeks 12, 24, 36, and 48 after randomization
Time frame
Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)4
Safety - Incidence of Adverse Events (AEs)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A serious AE is any AE occurring at any dose that - Results in death - Is life-threatening - Requires or prolongs existing inpatient hospitalization - Results in persistent or significant disability/incapacity - Is a congenital anomaly/birth defect - Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death.
Time frame
Weeks1--48Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Rongrong Liu
Lead sponsor
First Affiliated Hospital of Guangxi Medical University
Sponsor institution
Source ClinicalTrials.gov