Anemia, Sickle Cell
Conditions
Keywords
Hematologic Diseases, Anemia, Sickle Cell
Brief summary
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
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.
Interventions
DRUGMagnesium Pidolate, Hydroxyurea
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).
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 15 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed