Trial Information

Phase II Randomized Trial With A Modified Dose & Schedule of Subcutaneously Administered Azacitidine & Erythropoietin v Azacitidine Alone in Patients With Low-Risk Myelodysplastic Syndromes (Less Than 11% Marrow & Peripheral Blood Blasts)

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.