Combination of Thalidomide and Hydroxyuria in Transfusion Dependent Thalasemmia

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-01

Study Completion Date

2025-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Transfusion Dependent Beta Thalassemia

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Thalidomide, Hydoxyurea, Transfusion dependent thalassemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

ADDITION OF THALIDOMIDE AND HYDROXYUREA

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Hydrea and Thalidomide

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

2 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Professor Tariq Ghafoor

Director AFBMTC

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Tariq Ghafoor, FCPS,FRCP

Role: STUDY_DIRECTOR

National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

Locations

Explore where the study is taking place and check the recruitment status at each participating site.