The Efficacy of Combined Thalidomide and Hydroxyurea Therapy in Transfusion Dependent β-thalassemia (TDBT), Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 15
- 主要终点
- Number of Red Blood Cell Transfusions after starting a combination of Thalidomide and hydroxyurea
研究概览
简要总结
Beta thalassemia Major (BTM) is the most common hemoglobinopathy caused by mutations in the beta-globin gene . Worldwide, approximately 80 million people carry thalassemia gene mutation. Around 23,000 babies are affected by BTM each year, of which around 90% belong to low- or middle-income nations.
In Pakistan, the carrier prevalence of thalassemia is 5-7% resulting in a significant population of approximately 10 million carriers in the general population. There are 50,000 thalassemia patients registered in treatment facilities around the country, one of the highest global prevalence rates for transfusion dependent BTM. The average life expectancy of BTM patients in Pakistan is around 10 years of age, while life expectancy in developed countries is around 50 to 60 years. This difference is due to poor transfusion support, transfusion-transmitted infections (TTIs) and inadequate iron chelation leading to hepatotoxicity and cardiac failure.
The standard of care for BTM remains bone marrow transplantation or lifelong blood transfusions followed by iron chelation therapies. While standard care involves, challenges such as limited resources, lack of access to transplant services, and transfusion-related complications persist, particularly in low-and-middle-income countries.
详细描述
Beta thalassemia Major (BTM) is the most common hemoglobinopathy caused by mutations in the beta-globin gene . Worldwide, approximately 80 million people carry thalassemia gene mutation. Around 23,000 babies are affected by BTM each year, of which around 90% belong to low- or middle-income nations.
In Pakistan, the carrier prevalence of thalassemia is 5-7% resulting in a significant population of approximately 10 million carriers in the general population. There are 50,000 thalassemia patients registered in treatment facilities around the country, one of the highest global prevalence rates for transfusion dependent BTM. The average life expectancy of BTM patients in Pakistan is around 10 years of age, while life expectancy in developed countries is around 50 to 60 years. This difference is due to poor transfusion support, transfusion-transmitted infections (TTIs) and inadequate iron chelation leading to hepatotoxicity and cardiac failure.
The standard of care for BTM remains bone marrow transplantation or lifelong blood transfusions followed by iron chelation therapies. While standard care involves, challenges such as limited resources, lack of access to transplant services, and transfusion-related complications persist, particularly in low-and-middle-income countries.
Hydroxyurea (HU), an FDA-approved inducer of fetal hemoglobin (HbF), has shown promise in reducing or eliminating the need for frequent blood transfusions in β-thalassemia patients. However, a subset of patients exhibits limited responsiveness to HU, necessitating exploration of adjunct or alternative therapies. Thalidomide, an immune modulator, has demonstrated transfusion reduction by suppressing nuclear factor-κB induction, potentially increasing HbF levels.
The primary aim of this prospective study is to determine the efficacy of the combination of thalidomide and hydroxyurea in reducing transfusion frequency in patients with β-thalassemia Major. The secondary objectives are to document the spectrum of significant adverse drug reactions as well to document any alteration in the spleen size and serum ferritin levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients suffering from Transfusion Dependent β-thalassemia (TDBT) more than two years of age of either sex will be included in the study.
排除标准
- •Age less than two years.
- •Patients having cardiac, hepatic, pulmonary, renal or neurological dysfunction or history of thrombosis.
- •Both male and female participants of childbearing potential will be excluded due to the teratogenicity of thalidomide.
研究组 & 干预措施
A combination of thalidomide and hydroxyurea is added to patients diagnosed with TDT
- The trial include Hydroxyurea (HU) and Thalidomide in combination. The starting dose of Hydroxyurea will be 20 mg/kg once daily and of thalidomide will be 2.5-3 mg/kg once a day adjusted to nearest multiple of 10, at bedtime. Among those with partial response (PR) or no response (NR) after two months, the dose of thalidomide will be escalated in increments of 1 mg/kg/day at four weeks interval to a maximum of 5 mg/kg/day (maximum dose 100 mg/day).
- To prevent thrombosis, aspirin (2-4 mg/kg per day) will be used. All patients will receive Folic acid 2 to 5 mg once daily.
干预措施: ADDITION OF THALIDOMIDE AND HYDROXYUREA (Drug)
结局指标
主要结局
Number of Red Blood Cell Transfusions after starting a combination of Thalidomide and hydroxyurea
时间窗: 01 Year
The frequency of Red Blood cell transfusions before the start of intervention will be noted. At 03 months, 06 months, and 12 months of intervention (Thalidomide and hydroxyurea) number of Red Blood cell transfusions will be documented.
次要结局
- To assess changes in spleen size during the intervention.(01 Year)
- Monitoring of Serum Ferritin levels in ng/ml during the time of intervention.(01 Year)
- To document the spectrum and frequency of significant adverse drug reactions.(01 Year)
研究者
Professor Tariq Ghafoor
Director AFBMTC
Pakistan Blood and Marrow Transplant (PBMT) Group