OUTLINE: This is an open label, multi-center, randomized study.
Eligible patients will be randomized to one of two treatment arms:
Arm A (Azacitidine + Erythropoietin)
* Azacitidine Treatment 50 mg/m2 subcutaneously every other day (three times a week) for two consecutive weeks every four weeks. A cycle of therapy is defined as two consecutive weeks of subcutaneous azacitidine administered every other day three times a week (e.g. Monday - Wednesday - Friday) and the time to resolution of any treatment associated toxicity.
* Erythropoietin Treatment Patients who are randomized to Arm A will receive a dose of 60,000IU as a single subcutaneous injection weekly without interruption while enrolled on protocol therapy. The dose should be administered to coincide with the first day of each cycle.
* Protocol therapy may be administered for up to six cycles of therapy.
Arm B (Azacitidine Alone)
* Azacitidine Treatment 50 mg/m2 subcutaneously every other day (three times a week) for two consecutive weeks every four weeks. A cycle of therapy is defined as two consecutive weeks of subcutaneous azacitidine administered every other day three times a week (e.g. Monday - Wednesday - Friday) and the time to resolution of any treatment associated toxicity.
* Protocol therapy may be administered for up to six cycles of therapy.
ECOG performance status 0 to 2
Hematopoietic:
To be eligible for randomization, subjects must have documentation of at least 1 of the following:
* A transfusion dependent anemia (defined by a history of two or more episodes of transfusion within a period of 8 weeks).
* An untransfused hemoglobin \< 10 gm/dl measured on at least two occasions more than 7 days apart in the month prior to randomization.
Patients must also meet 1 of the following criteria:
* Has not received prior erythropoietin and has a serum erythropoietin level \> 200 IU/L within 14 days of randomization.
* Has received prior erythropoietin without clinical benefit in the judgment of the treating physician.
* Adequate iron status defined as serum ferritin \> 20 ng/ml and transferrin saturation of \> 30% within 90 days prior to randomization.
* Symptoms attributed to the anemia with hemoglobin \< 11 g/dL.
* Folate and Vitamin B12 levels within normal limits within 90 days prior to randomization.
Hepatic:
* SGOT (ALT) level \< 2 x ULN within 14 days prior to randomization.
* SGPT (AST) level \< 2 x ULN within 14 days prior to randomization.
* Serum total bilirubin level \< 2 x ULN within 14 days prior to randomization.
Renal:
* Serum creatine \< 1.5 x the upper limit of normal (ULN) within 14 days prior to randomization.
Cardiovascular:
* No uncontrolled hypertension (defined as a systolic pressure \> 160 mmHg and/or a diastolic pressure \> 110 mmHg).
* No history of (within 12 months) deep venous thrombosis (DVT), pulmonary embolism (PE), or other venous thrombosis. Prior superficial thrombophlebitis is not an exclusion criterion.
* No history of (within 6 months) cerebrovascular accident (\[CVA\] includes ischemic, embolic, and hemorrhagic), transient ischemic attack (TIA), myocardial ischemia (includes Unstable Angina, Q wave Myocardial Infarction \[QwMI\], and non-Q wave Myocardial Infarction \[NQMI\]), or other arterial thrombosis.
