Clinical Experience of Thalidomide in Thalassemic Patients

Study Overview
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Brief Summary
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Objectives Primary objective: • To determine the efficacy and safety of the combination therapy of Hydroxyurea and thalidomide in beta-thalassemia patients. Secondary objective: • To determine the change in liver and spleen size of beta-thalassemia patients on the combination therapy A single-arm non-randomized trial to evaluate the efficacy and safety of combination therapy of hydroxyurea and thalidomide in beta-thalassemia patients. It was a twelve months study. Participants were monitored for six months on Hydroxyurea alone and then the combination therapy of hydroxyurea and thalidomide for another six months. Findings of physical examination, vital signs, laboratory, and ultrasound findings were recorded at baseline, during and end of the study. Sample Size and Population This study included 135 Beta-thalassemia patients.

Detailed Description
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The purpose of the study was to evaluate the efficacy and safety of the combination therapy of hydroxyurea and thalidomide in beta-thalassemia patients. The participants were evaluated on the basis of eligibility criteria, consent was obtained and baseline investigations were performed on the screening visit. Participants were continued on Hydroxyurea (10-20mg/kg/day) for the first six months and then for the next six months thalidomide (2-5 mg/kg/day) was added to the intervention. Aspirin was also added (2-4mg/kg/day). Efficacy: Maintenance or rise in Hemoglobin (Hb) levels and changes in transfusion frequency before and after the use of combination therapy was used to evaluate the efficacy of the combination therapy. Good responders were the patients who were on transfusion and went off-transfusion after the combination therapy or individuals who were already off transfusion and after combination therapy demonstrated an increase in Hb of at least 1gm/dl. Responders were those who remained on transfusion on combination therapy but displayed a 50% reduction in blood requirements. Whereas, non-responders, were individuals who were off-transfusion before combination therapy and had improvement in Hb of <1gm/dl, or those who remained on transfusion during combination therapy and did not experience transfusion reduction of at least 50%. Safety: Safety of the drug was evaluated on the basis of the following parameters and intervention was discontinued or put on hold if: Creatinine >1.1mg/dl, Urea >43mg/dl), Liver function (SGPT >35mg/L) Absolute Neutrophil counts<2*109/L Platelets < 100*109/L

Official Title
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Efficacy and Safety of Combination of Hydroxyurea and Low-dose Thalidomide on Hemoglobin Synthesis in Thalassemia Patients

Conditions
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Thalassemia, Beta

Intervention / Treatment
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* Drug: hydroxyurea and thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinical and genetic diagnosis of β-thalassemia major and intermedia Patients who showed partial response or a decline in response to hydroxyurea Patients who are not the candidates for the bone marrow transplant procedure. Exclusion Criteria: Married Patients Patients with comorbidities such as liver, cerebrovascular, cardiovascular, or kidney diseases Patients allergic to the drug ingredients Patients with mental disorders Patients who are enrolled in other clinical trials Patients with a history of venous or arterial thrombosis

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination of hydroxyurea and thalidomide<br>Hydroxyurea was continued at a dose of 10-20 mg/kg/day for 6 months and then thalidomide was added orally at a dose of 2-5mg/kg/day for 6 months. | Drug: hydroxyurea and thalidomide<br>* Evaluation of hydroxyurea and thalidomide combination use in beta-thalassemia patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in transfusion requirements | Change in transfusion needs (measured as blood volume in ml) per month from baseline | 6 months on combination therapy | 
| Change in Hemoglobin levels | Change in hemoglobin level of >1g/dl from baseline | 6 months on combination therapy | 
| Change in the liver function test | Change in SGPT in U/l from baseline | 6 months on combination therapy | 
| Change in liver function test | Change in total, direct, and indirect bilirubin in mg/dl from baseline | 6 months on combination therapy | 
| Change in Kidney Function test | Change in urea and creatinine levels in mg/dl from baseline | 6 months on combination therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Spleen size | Change in size of spleen (in centimeters) from baseline | 6 months on combination therapy | 
| Change in liver size | Change in size of liver (in centimeters) from baseline | 6 months on combination therapy |