Phase I/II Randomized Study of Hydroxyurea With or Without Clotrimazole in Patients With Sickle Cell Anemia

PROTOCOL OUTLINE: This is a randomized study. Patients are randomized to one of two
treatment arms.

Arm I: Patients receive oral hydroxyurea and oral clotrimazole daily for 12 months.

Arm II: Patients receive oral hydroxyurea daily for 12 months. Patients are followed at 6
weeks.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of sickle cell anemia confirmed by hemoglobin electrophoresis

Received hydroxyurea for at least 6 months On a stable dose for at least 3 months
Tolerating dose of at least 5 mg/kg/day

--Prior/Concurrent Therapy--

Chemotherapy:

- No other concurrent antisickling agent

Other: No concurrent drug that may interact with or influence the metabolism of
hydroxyurea or clotrimazole

--Patient Characteristics--

Hematopoietic: WBC at least 4000/mm3 Platelet count at least 150,000/mm3 Hemoglobin less
than 11 g/dL

Hepatic: AST/ALT no greater than 100 units/L

Renal: Creatinine no greater than 1.5 mg/dL

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No prior adverse reaction to hydroxyurea or clotrimazole

- No recent or progressive neurologic dysfunction