Use of Hydroxyurea and Magnesium Pidolate for Treatment of Sickle Cell Disease

Study Overview
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Brief Summary
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The purpose of this study is to estimate the MTD of Mg pidolate in combination with HU in patients with sickle cell disease who have been on a therapeutic dose (15-30 mg/kg/day) of HU for at least 6 months.

Detailed Description
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This is a Phase I clinical trial evaluating the combination of hydroxyurea and magnesium pidolate for patients with sickle cell disease with either hemoglobin SS disease or hemoglobin S beta thalassemia. Hydroxyurea and magnesium pidolate will be tested in pediatric and adolescent patients with sickle cell disease who already have been treated with hydroxyurea for a minimum of six months. Magnesium pidolate will be given in combination with hydroxyurea for six months. In successive small groups of patients, the dose of magnesium will be increased in order to eventually determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) for magnesium when given in combination with hydroxyurea. The maximum tolerated dose is the highest drug dose that can be given safely to participants. The dose limiting toxicity is determined when drug side effects prevent an increase in dose.

Official Title
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Phase I Study of Combination Treatment With Hydroxyurea and Magnesium Pidolate in Patients With Sickle Cell Disease

Conditions
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Anemia, Sickle Cell

Intervention / Treatment
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* Drug: Magnesium Pidolate, Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 3 years and < 15 years at the time of study enrollment Diagnosis of Hb SS or Hb S beta thalassemia Hydroxyurea treatment for at least 6 months prior to study entry at dose of 15 - 30 mg/kg/day Compliance with taking HU treatment of at least 70 % for 6 months prior to study entry Exclusion Criteria: Red blood cell transfusion within the last 3 months resulting in a level of Hb A of 10% or more Pregnancy or unwillingness to use effective birth control in sexually active subjects (females who state that they are sexually active) Renal dysfunction defined by a serum creatinine greater than 1.5 times the upper limit of normal for age Liver dysfunction defined by an ALT greater than twice the upper limit of normal for age Concomitant usage of an antisickling agent other than hydroxyurea Current use of Mg containing drugs Iron deficiency, defined by serum ferritin ≤ 10 ng/ml Concomitant chronic illness other than sickle cell anemia

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 15 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 |
| --- | --- |
| Other: 1<br> | Drug: Magnesium Pidolate, Hydroxyurea<br>* Intervention Description: Mg pidolate in combination with HU in patients with sickle cell disease who have been on a therapeutic dose (15-30 mg/kg/day) of HU for at least 6 months. Mg pidolate will be given at an initial dose of 0.6 mEq/kg/day divided into 2 daily doses for the first cohort of patients. This dose will be escalated for the subsequent patient cohorts as defined by a classic Phase I design (according to toxicity).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the maximum tolerated dose of magnesium pidolate in combination with hydroxyurea in patients with sickle cell disease who have been on a therapeutic dose of hydroxyurea for at least six months. |  | Every 2 weeks for first 8 weeks; then every 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To document the toxicity of the combination of hydroxyurea and magnesium pidolate. |  | Every 2 weeks for first 8 weeks; then every 4 weeks | 
| To investigate the effect of the combination of hydroxyurea and magnesium on hematological parameters and red cell metabolism. |  | 3 months, 6 months, and 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematologic Diseases, Anemia, Sickle Cell