Conditions: Myelodysplastic Syndromes
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 15
Healthy volunteers: no

Brief summary:
This trial is designed to explore a modified dose and schedule of azacitidine in order to more effectively address the needs of patients with low-risk myelodysplastic syndromes (MDS), i.e., to alter the natural history of the disease without excessive toxicity or burden. The administration of erythropoietin is designed to influence the differentiation of primitive hematopoietic cells in which azacitidine has reversed the abnormal phenotype to red blood cells for patients in whom inadequate production of red blood cells is the major clinical issue.

Detailed description:
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.

Arms:
arm 1: Azacitidine + Erythropoietin arm 2: Azacitidine

Interventions: intervention 1: Azacitidine intervention 2: Erythropoietin intervention 3: Azacitidine (Monotherapy)
Intervention descriptions: intervention 1: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks. intervention 2: Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy intervention 3: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.

Protocol document: