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

Phase 2
Not Enrolling
Beta Thalassemia

Thank you

Trial Information

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

Individuals with homozygous beta-thalassemia are either severely anemic or dependent on
blood transfusion to sustain life. Deficient synthesis of the beta chain leads to
imbalanced chain synthesis with an excess of alpha globin. This alpha globin precipitates,
causing ineffective erythropoiesis and shortened red cell survival. In patients with
homozygous beta-thalassemia, enhanced gamma globin synthesis could partially compensate for
the deficient synthesis of beta globin rendering chain synthesis more balanced and reducing
the relative excess of alpha chains. The purpose of this protocol is to test the hypothesis
that induction therapy with 5-azacytidine, followed by maintenance treatment with oral
phenylbutyrate will enhance gamma globin synthesis, increase red cell production and
partially or substantially correct the anemia in patients with homozygous beta-thalassemia.

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

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

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.


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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

June 2000

Completion Date:

June 2003

Related Keywords:

  • Beta Thalassemia
  • Fetal Hemoglobin
  • 5-Azacytidine
  • Phenylbutyrate
  • Thalassemia
  • Hemoglobin
  • Anemia
  • Blood
  • Thalassemia Major
  • Beta Thalassemia
  • Beta-Thalassemia
  • Thalassemia



National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Bethesda, Maryland  20892