Safety and Efficacy of Hemoglobin F Inducers in Patients With Beta Thalassemia

Официальное название

Safety and Efficacy of Hemoglobin F Inducers in Patients With Beta Thalassemia: a Prospective 12 Months Study

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Thalidomide
  Tab Thalidomide 0.5 to 4 mg/kg orally every day for 12 months
• Препарат Hydroxy Urea
  Tab Hydroxyurea 10-20 mg/kg per day for 12 months

Первичные конечные точки

• Improvement in the hemoglobin level [Срок оценки: 6 months]
• Decrease in transfusion requirement [Срок оценки: 6 months]

Вторичные конечные точки (4)

• Serum Bilirubin levels [Срок оценки: 1 year]
• Change in ALT levels [Срок оценки: 1 year]
• Change in serum creatinine levels [Срок оценки: 1 year]
• Assess Quality of life by using EORTC QLQ-C30 [Срок оценки: 6 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Пакистан · 1 центр

• Riphah International University — Rawalpindi

Публикации

• Chen JM, Zhu WJ, Liu J, Wang GZ, Chen XQ, Tan Y, Xu WW, Qu LW, Li JY, Yang HJ, Huang L, Cai N, Wang WD, Huang K, Xu JQ, Li GH, He S, Luo TY, Huang Y, Liu SH, Wu WQ, Lu QY, Zhou MG, Chen SY, Li RL, Hu ML, Huang Y, Wei JH, Li JM, Chen SJ, Zhou GB. Safety and efficacy of thalidomide in patients with transfusion-dependent beta-thalassemia: a randomized clinical trial. Signal Transduct Target Ther. 202 PMID 34795208
• Ali Z, Ismail M, Rehman IU, Rani GF, Ali M, Khan MTM. Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent beta-thalassemia: results from Thal-Thalido study. Sci Rep. 2023 Aug 21;13(1):13592. doi: 10.1038/s41598-023-40849-4. PMID 37604857
• Tuo Y, Li Y, Li Y, Ma J, Yang X, Wu S, Jin J, He Z. Global, regional, and national burden of thalassemia, 1990-2021: a systematic analysis for the global burden of disease study 2021. EClinicalMedicine. 2024 May 6;72:102619. doi: 10.1016/j.eclinm.2024.102619. eCollection 2024 Jun. PMID 38745964
• Lu Y, Wei Z, Yang G, Lai Y, Liu R. Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ss-Thalassemia: A Meta-Analysis. Front Pharmacol. 2022 Jan 11;12:814302. doi: 10.3389/fphar.2021.814302. eCollection 2021. PMID 35087410
• Shah S, Sheth R, Shah K, Patel K. Safety and effectiveness of thalidomide and hydroxyurea combination in beta-thalassaemia intermedia and major: a retrospective pilot study. Br J Haematol. 2020 Feb;188(3):e18-e21. doi: 10.1111/bjh.16272. Epub 2019 Nov 11. No abstract available. PMID 31710694

Идентификаторы

NCT: NCT07673302 · Riphah/IIMC/IRB/26/1048

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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