Phase II Randomized Trial of Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of
two treatment arms. Arm I: Patients receive arginine butyrate IV over 6-9 hours at night 5
days a week for 12 weeks, plus concurrent standard local therapy consisting of cleaning,
saline irrigation, and dressing changes as prescribed by each patient's physician. Patients
who experience progressive healing receive arginine butyrate 3-4 times a week. Arginine
butyrate treatment may be discontinued and reinstated following a single 2 week medical
complication.

Arm II: Patients receive standard local therapy only for 12 weeks. Patients randomized to
arm II may cross over to receive arginine butyrate if no or less than 25% healing is
observed after 12 weeks.

Patients whose ulcers have closed by at least 15% per course may receive 2 additional 8-week
courses of arginine butyrate therapy and are followed for 2 months after healing is
completed.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Significant sickle cell syndrome including HbSS, S-beta
thalassemia, and hemoglobin variants Lower extremity or ankle ulcer (or ulcers) present
for at least 6 months without healing --Prior/Concurrent Therapy-- Biologic therapy: No
chronic transfusion therapy Chemotherapy: No prior or concurrent cancer chemotherapy No
concurrent butyrate derivatives Prior treatment with hydroxyurea allowed if on a stable
dose for at least 1 year Endocrine therapy: No concurrent corticosteroid therapy
Radiotherapy: Not specified Surgery: Not specified Other: Must be treated with antibiotics
prior to entry for complicating cellulitis or secondary infections --Patient
Characteristics-- Age: 16-60 Performance status: Not specified Hematopoietic: Not
specified Hepatic: No hepatic compromise Transaminases no greater than 250 IU Renal: No
renal compromise Creatinine no greater than 1.2 mg/mL (adults) Creatinine no greater than
0.9 mg/mL (teenagers) Other: Not pregnant Fertile patients must use effective
contraception No poorly controlled seizure disorders No other secondary conditions that
might inhibit immune function