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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Blood transfusion Group | No Intervention | Control group will be on regular blood transfusion and iron chelation therapy | |
| HbF inducers | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thalidomide | Drug | Tab Thalidomide 0.5 to 4 mg/kg orally every day for 12 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in the hemoglobin level | 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 | 6 months |
| Decrease in transfusion requirement | 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 | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Bilirubin levels | 0.2- 1.1 mg/dL Normal >1.1- 3 mg/dL Mild derangement >3 mg/dL Severe derangement | 1 year |
| Change in ALT levels | ALT levels range: 0- 42 U/L Normal >42-126 U/L Mild severity >126- 420 U/L Moderate severity >420 U/L severe |
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Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fariha Sardar, MBBS, FCPS | Contact | +923335517877 | doc.fariha@yahoo.com | |
| Fariha Sardar, MBBS, FCPS | Contact | +923350941494 | afzaal2kmt20@gamil.com |
| Name | Affiliation | Role |
|---|---|---|
| Fariha Sardar, MBBS, FCPS | Riphah International University, Rwp | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Riphah International University | Rawalpindi | Punjab Province | Pakistan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34795208 | Background | 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. 2021 Nov 18;6(1):405. doi: 10.1038/s41392-021-00811-0. | |
| 37604857 |
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| ID | Term |
|---|---|
| D013789 | Thalassemia |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D013792 | Thalidomide |
| D006918 | Hydroxyurea |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
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This is two-arm comparative study. One group is 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 occurred. The starting dose of hydroxyurea will be 10-20 mg/kg per day. Second group will be control group on Blood transfusion.
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| Hydroxy Urea | Drug | Tab Hydroxyurea 10-20 mg/kg per day for 12 months |
|
|
| 1 year |
| Change in serum creatinine levels | Serum creatinine 0.2 - 1.1 mg/dL Normal >1.1- 1.5 mg/dL Mild severity >1.5- 3.0 mg/dL Moderate severity >3 mg/dL Severe | 1 year |
| Assess Quality of life by using EORTC QLQ-C30 | EORTC QLQ C-30 URDU version, a self-administered questionnaire, will be filled by each participant at baseline and 6 months. Functional/Global: 100 = perfect function. 0 = no function. 10-point change = clinically meaningful. Symptoms: 0 = no symptoms. 100 = maximum symptoms 10-point increase = worse symptom burden. | 6 months |
| Background |
| 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. |
| 38745964 | Background | 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. |
| 35087410 | Background | 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. |
| 31710694 | Background | 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. |
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009930 |
| Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014508 | Urea |
| D000577 | Amides |