Phase II Study of Azacitidine and Phenylbutyrate in Patients With Thalassemia Major

OBJECTIVES:

I. Determine the safety and efficacy of azacitidine and phenylbutyrate in treatment of patients with thalassemia major.

PROTOCOL OUTLINE: Patients receive azacitidine IV continuously on days 1-4 and oral phenylbutyrate three times a day on days 14-42. Bone marrow needle aspiration is performed on days 6, 14, and 42 to assess disease response to treatment. If no response on day 42, a second course of azacitidine and phenylbutyrate begins 7 days later.

Patients are followed weekly for 3 months and then monthly thereafter.

• Drug: azacitidine
• Drug: phenylbutyrate

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of thalassemia major Progressive disease defined as: Increasing transfusion requirement or difficulty in maintenance of hemoglobin levels greater than 7 g/dL as a consequence of autologous or allogeneic antibodies OR Increasing extramedullary hematopoiesis causing compression phenomena OR Disease with complications of iron overload despite traditional transfusion and iron chelation therapy (e.g., heart failure, decreased cardiac ejection fraction, endocrinopathy, or evidence of progressive liver dysfunction)

Standard transfusion therapy or iron chelation therapy must be contraindicated

--Prior/Concurrent Therapy--

See Disease Characteristics

--Patient Characteristics--

Performance status: ECOG 0-2

Life expectancy: Greater than 10 days Not moribund

Hematopoietic: See Disease Characteristics

Hepatic: See Disease Characteristics AST or ALT no greater than 3 times upper limit of normal (ULN) Bilirubin no greater than 1.5 times ULN (unless due to hemolysis or Gilbert's disease) Albumin at least 3 g/dL No severe concurrent hepatic disease

Renal: Creatinine no greater than 2 mg/dL Creatinine clearance at least 60 mL/min No severe concurrent renal disease

Cardiovascular: See Disease Characteristics No New York Heart Association class III or IV

Other: Not pregnant or nursing No severe concurrent metabolic disease No severe sepsis or septic shock No concurrent altered mental status or seizure disorder No concurrent myelodysplastic syndrome or leukemia