Combination of Thalidomide and Hydroxyuria in Transfusion Dependent Thalasemmia (Thal-H)

April 29, 2026 updated by: Professor Tariq Ghafoor, Pakistan Blood and Marrow Transplant (PBMT) Group

The Efficacy of Combined Thalidomide and Hydroxyurea Therapy in Transfusion Dependent β-thalassemia (TDBT), Phase II Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Punjab Province
      • Islamabad, Punjab Province, Pakistan, 46000
        • Armed Forces Bone Marrow Transplant Center
      • Rawalpindi, Punjab Province, Pakistan, 44000
        • Armed Forces Bone Marrow Transplant Center
      • Rawalpindi, Punjab Province, Pakistan, 46000
        • AFBMTC (Clinical Trial and Research Cell)
      • Rawalpindi, Punjab Province, Pakistan, 46000
        • AFBMTC (CT&RC), CMH Medical Complex
      • Rawalpindi, Punjab Province, Pakistan, 46000
        • AFBMTC (CT&RC), Medical Complex
      • Rawalpindi, Punjab Province, Pakistan, 46000
        • AFBMTC, CMH Medical Complex
      • Rawalpindi, Punjab Province, Pakistan, 46000
        • Armed Forces Bone Marrow Transplant Center Rawalpindi Pakistan
      • Rawalpindi, Punjab Province, Pakistan, 46000
        • Armed Forces Bone Marrow Transplant Center
      • Rawalpindi, Punjab Province, Pakistan, 60000
        • Armed Forces Bone Marrow Transplant Center Rawalpindi Pakistan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

• Patients suffering from Transfusion Dependent β-thalassemia (TDBT) more than two years of age of either sex will be included in the study.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: ADDITION OF THALIDOMIDE AND HYDROXYUREA

The intervention includes 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.
  • Patients will also continue the iron chelation therapy (Deferasirox, Deferiprone or Deferoxamine) in case of iron overload.
Other Names:
  • Hydrea and Thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Red Blood Cell Transfusions after starting a combination of Thalidomide and hydroxyurea
Time Frame: 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.
01 Year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To document the spectrum and frequency of significant adverse drug reactions.
Time Frame: 01 Year

Monitoring and recording any adverse effects associated with thalidomide and hydroxyurea therapy at Day-90, Day-180, and Day-365.

Patients will be contacted on the telephone weekly by the drug safety monitoring board and will be screened for any side effects of the intervention.
01 Year
To assess changes in spleen size during the intervention.
Time Frame: 01 Year
Assessment of spleen size in centimeters at Day-01, Day-90, Day-180, and Day-365 of intervention.
01 Year
Monitoring of Serum Ferritin levels in ng/ml during the time of intervention.
Time Frame: 01 Year
Measurement of Serum Ferritin Levels in ng/ml at Day-01, Day-90, Day-180, and Day-365.
01 Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pakistan Blood and Marrow Transplant (PBMT) Group

Investigators

  • Study Director: Tariq Ghafoor, FCPS,FRCP, National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2024

Primary Completion (Actual)

December 30, 2025

Study Completion (Actual)

December 30, 2025

Study Registration Dates

First Submitted

November 13, 2025

First Submitted That Met QC Criteria

December 5, 2025

First Posted (Actual)

December 18, 2025

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

April 29, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PBMT-1
  • 6871 (Other Identifier: AFBMTC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The investigators may share de-identified IPD upon reasonable request, beginning 9 months after publication and available for up to 24 months, following review and data-sharing agreement.

IPD Sharing Time Frame

Six months after completion of study

IPD Sharing Access Criteria

Contact with PI

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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