EXTEND EXpanding Treatment for Existing Neurological Disease

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary goal of the Phase II EXTEND trial is to investigate the effects of open-label hydroxyurea treatment, escalated to maximum tolerated dose, for children with Sickle Cell Anemia and either conditional (170 - 199 cm/sec) or abnormal (≥200 cm/sec) Transcranial Doppler velocities. The primary endpoint will be measured after 18 months of hydroxyurea but treatment will continue until a common study termination date.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Caribbean Institute for Health Research (CAIHR); Tropical Medicine Research Institute
• Treatments: Hydroxyurea

Criteria

Inclusion Criteria:

1. Pediatric participants with a severe form of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab)

2. Age: ≥ 2 and ≤ 17 years of age, at the time of enrollment

3. Time-averaged maximum velocity (TAMV) TCD Velocity in the conditional (170 - 199 cm/sec) or abnormal (≥200 cm/sec) range by Transcranial Doppler ultrasonography examination within 6 months of enrollment, abnormal or conditional TCD velocity and currently on commercial hydroxyurea for primary stroke prevention, or previously enrolled in SCATE, a previous stroke with abnormal or conditional TCD prior to stroke event.

4. Parent or guardian willing and able to provide informed consent and child gives assent

5. Ability to comply with study related treatments, evaluations, and follow- up visits

Exclusion Criteria:

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

• Known allergy to hydroxyurea therapy

• Known positive serology to HIV infection

• Known malignancy

• Current lactation

2. Abnormal historical laboratory values (most recent pre-enrollment values unless previously enrolled in SCATE):

• Hemoglobin concentration < 6.0 gm/dL

• Absolute reticulocyte count < 100 x 109/L with a hemoglobin concentration < 8.0 gm/dL

• White Blood Cell (WBC) count < 3.0 x 109/L

• Absolute neutrophil count (ANC) < 1.0 x 109/L

• Platelet count < 100 x 109/L

3. Use of therapeutic agents for sickle cell disease (e.g., hydroxyurea, arginine, decitabine, magnesium, chronic transfusions) within 3 months of enrollment unless they have an abnormal TCD velocity and receive commercial hydroxyurea for primary stroke prevention or were previously enrolled in the SCATE study or for secondary stroke prevention in a child with a previous stroke.

4. Current participation in other therapeutic clinical trials, except SCATE

5. Known serum creatinine more than twice the upper limit for age AND

• 1.0 mg/dL

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

7. Pregnancy (for post-menarchal females only)

8. Erythrocyte transfusion within the past 2 months

9. Previous stem cell transplant or other myelosuppressive therapy (unless they have an abnormal TCD velocity and receive commercial hydroxyurea for primary stroke prevention or for secondary stroke prevention in a child with a previous stroke or were previously enrolled in SCATE)