inability to reach a satisfactory endpoint with respect to adequate recruitment

The primary goal of the Phase III SCATE trial is to compare 30 months of alternative therapy (hydroxyurea) to standard care (observation) in children with sickle cell anemia and conditional (170 - 199cm/sec) Transcranial Doppler (TCD) velocities. For the alternative regimen (hydroxyurea) to be declared superior to the standard treatment regimen (observation), the hydroxyurea-treated group must have a three-fold reduction in the incidence of conversion to abnormal TCD velocities (≥ 200 cm/sec), compared to the standard treatment arm.

Results from previous studies confirm an increased risk of stroke among children with conditional TCD velocities. In addition, studies suggest that patients who were on observation alone, converted from conditional TCD (moderate risk category) to an abnormal TCD (with a much higher risk for primary stroke) within 30 months of initial identification of the conditional TCD velocity; this conversion led to initiation of chronic and indefinite transfusions in all cases. Preliminary data suggests that the risk of conversion to abnormal TCD velocities will be lower for subjects with conditional TCD velocities on hydroxyurea by at least three-fold. This important difference in conversion risk rate suggests that an alternative treatment could have a substantial and beneficial impact on patients with elevated TCD velocities.

An alternative treatment could protect the brain of patients with SCA and conditional TCD velocities who are at increased risk for stroke. The avoidance of chronic blood transfusions would be a great benefit for all children with sickle cell disease, especially those in developing countries where the blood supply may be less safe (in comparison with that in the US) or unavailable, and very costly.

Inclusion Criteria:

1. Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)
2. Age: ≥ 2 and < 11 years of age, at the time of enrollment
3. Conditional TCD Velocity (170 - 199cm/sec) by Transcranial Doppler ultrasonography examination within 3 months of enrollment
4. Parent or guardian willing and able to provide informed consent
5. Ability to comply with study related treatments, evaluations, and follow-up

Exclusion Criteria:

1. Prior abnormal TCD Velocity

2. History of clinical stroke

3. Inability to take or tolerate daily oral hydroxyurea, including

   • Known allergy to hydroxyurea therapy
   • Known positive serology to HIV infection
   • Known malignancy
   • Current lactation

4. Abnormal laboratory values at initial evaluation (temporary exclusions):

   • Hemoglobin concentration < 6.0 gm/dL
   • Absolute reticulocyte count < 100 x 10^9/L with a hemoglobin concentration < 8.0 gm/dL
   • WBC count < 3.0 x 10^9/L
   • Absolute neutrophil count (ANC) < 1.0 x 10^9/L
   • Platelet count < 100 x 10^9/L

5. Current use of therapeutic agents for sickle cell disease (e.g., hydroxyurea, arginine, decitabine, magnesium, chronic transfusions). Subjects must be off therapeutic agents for sickle cell disease for at least 3 months prior to enrollment.

6. Current participation in other therapeutic clinical trials

7. Serum creatinine more than twice the upper limit for age OR ≥ 1.0 mg/dL

8. Any condition or chronic illness, which in the opinion of the clinical investigator makes participation ill-advised

9. Pregnancy (for post-menarchal females only)

10. Erythrocyte transfusion within the past 2 months

11. Previous stem cell transplant or other myelosuppressive therapy

May 2012 - Jan 2014 = 20 months

AEs below grade 2 were not recorded for the SCATE trial