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

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

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.

Study Overview

• Status: Unknown
• Conditions: Thalassemia Intermedia
• Intervention / Treatment: Drug: hydroxyurea, blood transfusion; Drug: Hydroxyurea ,Epiao

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • hematology clinic ,pediatrics hospital, Ain Shams University hospital
    • Principal Investigator: Mohsen Saleh El-Alfy, professor of pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Hydroxyurea,blood transfusion; 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; 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.
EXPERIMENTAL: Hydroxyurea, Epiao; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ain Shams University

Publications and helpful links

General Publications

• Elalfy MS, Adly AA, Ismail EA, Elhenawy YI, Elghamry IR. Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young beta-thalassemia intermedia patients. Eur J Haematol. 2013 Dec;91(6):522-33. doi: 10.1111/ejh.12182. Epub 2013 Oct 5.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2012
• Study Completion (ANTICIPATED): December 1, 2012

Study Registration Dates

• First Submitted: April 13, 2012
• First Submitted That Met QC Criteria: June 18, 2012
• First Posted (ESTIMATE): June 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 20, 2012
• Last Update Submitted That Met QC Criteria: June 18, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Hydroxyurea; Erythropoitin therapy; Thalassemia intermedia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: huoepio