Safety and Efficacy of Hemoglobin F Inducers in Patients With Beta Thalassemia: a Prospective 12 Months Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Improvement in the hemoglobin level
研究概览
简要总结
The aim of this study is to determine the safety and therapeutic effect of HbF inducers (combination therapy: thalidomide and hydroxyurea) on beta thalassemia patients. The main objectives of this study are:
- To determine the therapeutic efficacy of HbF inducers (combination therapy: thalidomide and hydroxyurea) on hemoglobin level and blood transfusion in beta thalassemia patients.
- To determine the safety of HbF inducers (combination therapy: thalidomide and hydroxyurea) in beta thalassemia patients
- To determine effect of HbF inducers (combination therapy: thalidomide and hydroxyurea) on quality of life of beta thalassemia patients
详细描述
This is a two-arm comparative study. One group is the interventional group, in which all patients will receive thalidomide and hydroxyurea. Low-dose Thalidomide will be administered to patients at a low dose of 0.5 to 4 mg/kg orally every day for 12 months until continuous transfusion-dependency or unacceptable toxicity occurs. The starting dose of hydroxyurea will be 10-20 mg/kg per day. The second group will be the control group for blood transfusion.
In the intervention group, 114 confirmed diagnoses of beta thalassemia ascertained by Hemoglobin Electrophoresis or HPLC report performed pre-transfusion or genetic testing profile (comprising PCR or HBB gene sequencing) suggestive of β-thalassemia syndrome will be included. To assess the therapeutic efficacy of HbF inducers (combination therapy: thalidomide and hydroxyurea), the number of blood transfusions and hemoglobin level will be assessed as per the given schedule.
. Adverse events will be recorded at each follow-up to assess the safety of the therapy. The patient/guardian/parent will be specifically asked about paresthesia, rash, constipation, unexplained infections, bleeding symptoms, headache, syncope, focal weakness, and behavioral changes. All participants will be asked to report any adverse reactions and will be questioned about adverse events during the study visit. EORTC QLQ C-30 URDU version, a self-administered questionnaire, will be filled by each participant at baseline and 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of Beta thalassemia Major (BTM) ascertained by Hemoglobin Electrophoresis or HPLC report performed pre-transfusion or genetic testing profile (comprising PCR or HBB gene sequencing) suggestive of β-thalassemia syndrome.
- •All ages and both genders will be included
- •Written informed consent
排除标准
- •Pregnancy or unwilling to follow contraception or planning conception (Enrolled female patients will be strictly advised to avoid pregnancy during the study period and until 6 months after thalidomide withdrawal.
- •Hemoglobinopathies other than beta thalassemia
- •History of neurological problems
- •Inability to regularly follow up
研究组 & 干预措施
Blood transfusion Group
Control group will be on regular blood transfusion and iron chelation therapy
HbF inducers
All patients will receive thalidomide and hydroxyurea. Low dose Thalidomide will be administered to patients at a low dose of 0.5 to 4 mg/kg orally every day for 12 months until continuous transfusion-dependency or unacceptable toxicity occurred. The starting dose of hydroxyurea will be 10-20 mg/kg per day.
干预措施: Hydroxy Urea (Drug)
HbF inducers
All patients will receive thalidomide and hydroxyurea. Low dose Thalidomide will be administered to patients at a low dose of 0.5 to 4 mg/kg orally every day for 12 months until continuous transfusion-dependency or unacceptable toxicity occurred. The starting dose of hydroxyurea will be 10-20 mg/kg per day.
干预措施: Thalidomide (Drug)
结局指标
主要结局
Improvement in the hemoglobin level
时间窗: 6 months
To evaluate the Improvement in Hemoglobin level, response criteria are defined as follows: Major response, an elevation in total Hb level of ≥2 g/dL Minor response, an elevation in total Hb level of 1 to 2 g/dL, or Hb not substantially increased (\<1 g/dL) but the patients achieve Hb\>7 g/L No response, an elevation in total Hb level of \<1 g/dL
Decrease in transfusion requirement
时间窗: 6 months
To evaluate the decrease in transfusion requirement, response criteria are defined as follows: Major response: reduce transfusion requirements by ≥25% after 6 months of therapy compared to baseline. Minor response: reduce transfusion requirement by \<25 % after 6 months of therapy, No response: same blood transfusion requirement as baseline
次要结局
- Serum Bilirubin levels(1 year)
- Change in ALT levels(1 year)
- Change in serum creatinine levels(1 year)
- Assess Quality of life by using EORTC QLQ-C30(6 months)