A Pilot Study of 5-Azacytidine and Oral Sodium Phenylbutyrate in Severe Thalassemia

Inclusion Criteria

INCLUSION CRITERIA:

Thalassemia major with progressive disease or complications of iron overload despite
traditional transfusion and iron chelation therapy

Thalassemia major in which standard transfusion therapy or iron chelation therapy is
contraindicated

ECOG performance status must be less than or equal to 2

NYHA less than or equal to class II status

Progressive disease is defined as 1) an increasing transfusion requirement or difficulty
in maintenance of hemoglobin levels greater than 7g/dl as a consequence of autologous or
allogeneic antibodies or 2) increasing extramedullary hematopoiesis causing compression
phenomena.

Complications of iron overload despite iron chelation therapy is defined as difficulty in
achieving negative iron balance when complications of iron overload exist. Complications
of iron overload include heart failure, or decreased cardiac ejection fraction,
endocrinopathy and evidence of progressive liver dysfunction.

EXCLUSION CRITERIA:

Severe sepsis or septic shock

Current pregnancy or breast feeding

Not able to give informed consent

Altered mental status or seizure disorder

AST or ALT greater than 3X upper limit of normal

Bilirubin greater than1.5X upper limit of normal, unless the abnormal bilirubin can be
accounted for by indirect hyperbilirubinemia due to hemolysis or Gilbert's Disease

Serum albumin less than 3g/dl

Creatinine greater than 2mg/dl and creatinine clearance less than 60ml/min

Patients who are moribund or patients with concurrent hepatic, renal, cardiac, metabolic,
or any disease of such severity that death within 7-10 days is likely

Concurrent myelodysplastic syndrome or leukemia

NYHA class III/IV status

ECOG performance status greater than 2

Age less than 18 years