Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effectiveness of Hydroxyurea and Magnesium Pidolate Alone and in Combination in Hemoglobin SC Disease: A Phase II Trial
Brief Summary: Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause intense pain episodes. Hemoglobin SCD (HbSC) is a form of SCD that is characterized by dense red blood cells. The purpose of this study is to evaluate the safety and effectiveness of hydroxyurea and magnesium pidolate, alone and combined, at reducing red blood cell density and the frequency of pain episodes in people with HbSC.


Options:
A: Inclusion Criteria:

* Children with confirmed SCA who participated in the NOHARM study of hydroxyurea at the Mulago Hospital Sickle Cell Clinic (MHSCC), will be eligible for the MTD study after completing both 12-months of blinded study treatment and then an additional 12-months of open-label hydroxyurea for the second year of the study.
* The age range for enrollment into NOHARM, which began in 2014, was 1-4 years. Therefore, the children who will be enrolled in the follow up MTD study will be 3-6 years of age.

Exclusion Criteria:

* Not willing to come for all scheduled clinical visits or accept randomization
B: Inclusion Criteria:

* Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSOArab)
* Age range of 5.0-18.9 years, inclusive, at the time of study entry
* Initial (primary) completed overt clinical stroke after the age of one year (12 months) with documented infarction on brain computed tomography (CT) or magnetic resonance imaging (MRI)
* At least 18 months of chronic monthly erythrocyte transfusions since primary stroke
* Transfusional iron overload, defined as a previously documented liver iron concentration (LIC) greater than or equal to 5.0 mg Fe per gram of dry weight liver or serum ferritin greater than or equal to 500 ng/mL on two independent measurements
* Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45% (the upper limit of the established academic community standard) in the 6 months prior to study entry
* Parent or guardian willing and able to provide informed consent with verbal or written assent from the child (less than 18 years of age) or subject willing and able to provide informed consent (older than 18 years of age)
* Ability to comply with study-related treatments, evaluations, and follow-up

Exclusion Criteria:

* Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following:

  1. Multiple RBC alloantibodies making cross-matching difficult or impossible
  2. RBC autoantibodies making cross-matching difficult or impossible
  3. Religious objection to transfusions that preclude their chronic use
  4. Non-compliance with transfusions in the 6 months prior to study entry (temporary exclusion)
* Inability to take or tolerate daily oral hydroxyurea, due to any of the following:

  1. Known allergy to hydroxyurea therapy
  2. HIV infection
  3. Cancer
  4. Pregnant or breastfeeding
  5. Previous stem cell transplant or other myelosuppressive therapy
* Clinical and laboratory evidence of hypersplenism, due to any of the following:

  1. Palpable splenomegaly greater than 5 cm below the left costal margin and
  2. Transfusion requirement greater than 250 mL/kg in the 12 months prior to study entry
* Abnormal laboratory values at initial evaluation (temporary exclusion):

  1. Pre-transfusion hemoglobin concentration less than 7.0 gm/dL
  2. White blood cell (WBC) count less than 3.0 x 109/L
  3. Absolute neutrophil count (ANC) less than 1.5 x 109/L
  4. Platelet count less than 100 x 109/L
  5. Serum creatinine more than twice the upper limit for age OR greater than or equal to 1.0 mg/dL
* Current participation in other therapeutic clinical trials
* Current use of other therapeutic agents for SCA (e.g., arginine, decitabine, magnesium)
* Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in the opinion of the study physician makes study participation ill-advised
* Inability or unwillingness to complete required screening studies, including blood tests, brain MRI/magnetic resonance angiography (MRA), and liver biopsy
* A sibling enrolled in SWiTCH
C: Inclusion Criteria:

* Pediatric subjects with documented sickle cell anemia (HbSS supported by hemoglobin electrophoresis or by peripheral blood smear showing sickled red blood cells)
* Age range of 1.00-3.99 years, inclusive, at the time of enrollment
* Weight at least 5.0 kg at the time of enrollment
* Willingness to comply with all study-related treatments, evaluations, and follow up

Exclusion Criteria:

* Known chronic medical condition (e.g., HIV, malignancy, active clinical tuberculosis)
* Severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or weight-for-length/height \> 3 z-scores below the median WHO growth standards)
* Pre-existing severe hematological toxicity:

  1. Hb \<4.0 g/dL
  2. Hb \<6.0 g/dL AND ARC \<100 x 10E9/L
  3. Hb \<7.0 g/dL AND ARC \<80 x 10E9/L
  4. Platelets \<80 x 10E9/L
  5. ANC \<1.0 x 10E9/L
* Alanine transaminase (ALT) or creatinine \>2 times the upper limit of normal for age
* Blood transfusion within 30 days prior to enrollment
D: Inclusion Criteria:

* Diagnosis of HbSC disease
* Hemoglobin level between 8 and 12.5 g/dL
* At least one vaso-occlusive event (e.g., pain, acute chest syndrome) in the 12 months prior to study entry. An episode of pain is defined as the occurrence of pain in the extremities, back, abdomen, chest, or head that lasts at least 2 hours; requires a visit to a hospital, emergency room, clinic, or provider's office; and is not explained except by SCD. Acute chest syndrome is defined as a new pulmonary infiltrate on a chest x-ray associated with a fever (greater than 38.5° C), tachypnea, wheezing, cough, or chest pain.
* Regular compliance with comprehensive care
* In a steady disease state and not experiencing an acute complication of SCD (i.e., no hospitalization, pain event, or episode of acute chest syndrome within the 1 month prior to study entry)

Exclusion Criteria:

* Previous transfusion with remaining hemoglobin A greater than 10%
* Previous treatment with hydroxyurea within the last 3 months
* Previous treatment with magnesium within the 3 months prior to study entry (including vitamins containing magnesium)
* Poor compliance with previous treatment regimens
* Liver dysfunction (SGPT greater than twice the upper limit of normal) within the 1 month prior to study entry
* Kidney dysfunction (creatinine greater than or equal to 1.0 mg/dL for participants less than 18 years of age; greater than or equal to 1.2 mg/dL for participants 18 years of age or older) within the 1 month prior to study entry
* Pregnant
* Ten or more hospital admissions for pain in the 12 months prior to study entry
* Daily use of narcotics
* Treatment with any investigational drug in the 3 months prior to study entry
* Less than 3% red blood cells with density greater than 41 g/dL (as measured by the ADVIA 120 system)
* Positive HIV test
* Other long-term illness or disorder other than SCD that could adversely affect performance in the study (e.g., tuberculosis)

Answer: D