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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Thalassemia
• Intervention / Treatment: Drug: Thalidomide; Drug: Hydroxy Urea

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fariha Sardar, MBBS, FCPS; Phone Number: +923335517877; Email: doc.fariha@yahoo.com
• Study Contact Backup: Name: Fariha Sardar, MBBS, FCPS; Phone Number: +923350941494; Email: afzaal2kmt20@gamil.com

Study Locations

• Pakistan
  • Punjab Province
    • Rawalpindi, Punjab Province, Pakistan
      • Riphah International University
      • Contact: Fariha Sadar, MBBS, FCPS; Phone Number: +923335517877; Email: doc.fariha@yahoo.com
      • Contact: Fariha Saradr, MBBS, FCPS; Phone Number: +923350941494; Email: afzaal2kmt20@gamil.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• 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

Exclusion criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Blood transfusion Group; Control group will be on regular blood transfusion and iron chelation therapy
Experimental: 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.	Drug: Thalidomide; Tab Thalidomide 0.5 to 4 mg/kg orally every day for 12 months; Other Names: Thalido; Drug: Hydroxy Urea; Tab Hydroxyurea 10-20 mg/kg per day for 12 months; Other Names: Hydrea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Riphah International University
• Investigators: Principal Investigator: Fariha Sardar, MBBS, FCPS, Riphah International University, Rwp

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 19, 2027
• Study Completion (Estimated): June 19, 2027

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Thalassemia; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Amides; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Urea; Thalidomide; Hydroxyurea
• Other Study ID Numbers: Riphah/IIMC/IRB/26/1048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No