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

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

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.

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.

Inclusion Criteria:

1. Age > 3 years and < 15 years at the time of study enrollment
2. Diagnosis of Hb SS or Hb S beta thalassemia
3. Hydroxyurea treatment for at least 6 months prior to study entry at dose of 15 - 30 mg/kg/day
4. Compliance with taking HU treatment of at least 70 % for 6 months prior to study entry

Exclusion Criteria:

1. Red blood cell transfusion within the last 3 months resulting in a level of Hb A of 10% or more
2. Pregnancy or unwillingness to use effective birth control in sexually active subjects (females who state that they are sexually active)
3. Renal dysfunction defined by a serum creatinine greater than 1.5 times the upper limit of normal for age
4. Liver dysfunction defined by an ALT greater than twice the upper limit of normal for age
5. Concomitant usage of an "antisickling" agent other than hydroxyurea
6. Current use of Mg containing drugs
7. Iron deficiency, defined by serum ferritin ≤ 10 ng/ml
8. Concomitant chronic illness other than sickle cell anemia