Therapeutic Effect and Safety of Combined Hydroxyurea With Recombinant Human Erythropoietin.

Study Overview
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Brief Summary
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The study hypothesis that treatment with Erythropoietin (EPO) combined with Human Erythropoietin (HUO) therapy will result in hematologic improvement in thalassemia intermedia patients. Second is to determine whether any of the following correlate with improved hematologic response: A decrease in hemolysis, as assayed by a decrease in LDH, compared to baseline levels,baseline Erythropoietin levels,baseline hemoglobin levels and baseline reticulocyte counts (or % circulating nucleated erythroblasts/100 WBCs). Goal: The aim is to assess the possibility of steady increase of hemoglobin levels in thalassemia intermedia patients by at least 1g/dl above baseline levels during therapy using Hydroxyurea and Erythropoietin, growth evaluation,quality of life (QoL) and decline transfusion requirements during study period. Also to report and compare adverse events with other published data regarding.

Detailed Description
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To determine whether any of the following correlate with improved hematologic response: A decrease in hemolysis, as assayed by a decrease in LDH, compared to baseline levels,baseline Erythropoietin levels,baseline hemoglobin level and baseline reticulocyte counts (or % circulating nucleated erythroblasts/100 WBCs). To assess the possibility of steady increase of hemoglobin levels in thalassemia intermedia patients by at least 1g/dl above baseline levels during therapy using Hydroxyurea and Erythropoietin, growth evaluation , quality of life ( QoL ) and decline transfusion requirements during study period. Also to report and compare adverse events with other published data regarding. THE following criteria are used when including the patient in the study: Patients with thalassemia intermedia.Diagnosis based on genetic mutations, hemoglobin electrophoresis and characteristic clinical data at presentation. Patients requiring different transfusion requirements and not transfusion dependent.Patients having a baseline hemoglobin of less than or equal to 6-8g/dl.Patients with normal renal and liver function.

Official Title
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Phase 2 Study of Therapeutic Effect and Safety of Combined Hydroxyurea With Recombinant Human Erythropoietin.

Conditions
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Thalassemia Intermedia

Intervention / Treatment
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* Drug: Hydroxyurea ,Epiao
* Drug: hydroxyurea, blood transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with thalassemia intermedia. Diagnosis based on genetic mutations, hemoglobin electrophoresis and characteristic clinical data at presentation. Require different transfusion requirements and not transfusion dependent. Have a baseline hemoglobin of less than or equal to 6-8g/dl. Patients with normal renal and liver function. Exclusion Criteria: Evidence of active hepatitis (ALT > 5 times above ULN). Evidence of renal impairment (serum creatinine > ULN). Patients who are dependent on red blood cell transfusions.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxyurea,blood transfusion<br>Hydroxyurea (Myers-Squibb, USA) was administered in dosages ranging from 15 up to 35 mg/kg/day orally over 7 days/week. | Drug: hydroxyurea, blood transfusion<br>* Hydroxyurea was administered in dosages ranging from 15 up to 35 mg/kg/day orally over 7 days/week. Hydroxyurea toxicity was defined as a white cell count of less than 2500/μL or a platelet count of less than 100,000/μL, in which case the drug was discontinued.<br>|
| Experimental: Hydroxyurea, Epiao<br>Hydroxyurea (Myers-Squibb, USA) was administered in dosages ranging from 15 up to 35 mg/kg/day orally over 7 days/week. Hydroxyurea toxicity was defined as a white cell count of less than 2500/μL or a platelet count of less than 100,000/μL, in which case the drug was discontinued. White cell count and platelet count were determined on a monthly basis. Side effects such as nausea, vomiting, diarrhea, rashes, and malaise, experienced during the first 6 h after taking the HU will be considered as clinical toxicity. Erythropiotien therapy (rHuEPO - Epiao) from 250 to 500 IU/kg rHuEPO subcutaneously three times a week. | Drug: Hydroxyurea ,Epiao<br>* Hydroxyurea (Myers-Squibb, USA) was administered in dosages ranging from 15 up to 35 mg/kg/day orally over 7 days/week. Erythropiotien therapy (rHuEPO - Epiao) from 250 to 500 IU/kg rHuEPO subcutaneously three times a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in baseline transfusion frequency with increase of pre-transfusion hemoglobin | Decrease in baseline transfusion frequency with increase of pre-transfusion hemoglobin by calculation of transfusion index and mean hemoglobin level | baseline and 6 month hemoglobin level and transfusion frequency | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in baseline quality of life assessment. | Quality of life assessment using (QOL questionaire) at the begining and at 6 month | baseline and 6 month QOL questionaire | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxyurea, Erythropoitin therapy, Thalassemia intermedia