Azacitidine and Erythropoietin Versus Azacitidine Alone for Patients With Low-Risk Myelodysplastic Syndromes
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Azacitidine; Erythropoietin; Azacitidine (Monotherapy)
Intervention description: Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.; Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy; Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Intervention MeSH terms: Azacitidine; Epoetin Alfa
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A bone marrow (BM) aspirate and biopsy that demonstrates MDS with less than 11%
             blasts.

          -  Conventional metaphase cytogenetics done within 90 days prior to registration for
             screening.

          -  Central pathology review, correlative submission and confirmation of diagnosis is
             required prior to initiation of therapy (see Study Procedure Manual for details of
             submission). The FAB and WHO classification of MDS and the IPSS score will be
             determined at time of central pathology review.

          -  Correlative marrow aspirate obtained.

        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.

          -  Life expectancy > 6 months as judged by the treating investigator.

        Exclusion Criteria:

          -  No known history of intolerance to erythropoietic agents.

          -  No prior intensive cytotoxic chemotherapy for a myeloid malignancy including MDS.

          -  Patients with a history of a non-myeloid malignancy with secondary MDS are eligible
             for study enrollment provided, in the opinion of the treating investigator and the
             study chair, the anticipated behavior of the non-myeloid malignancy will not interfere
             with study participation and evaluation of outcome.

          -  No known or suspected hypersensitivity to azacitidine or mannitol.

          -  No hepatic tumors.

          -  No uncontrolled hypertension (defined as a systolic pressure > 160 mmHg and/or a
             diastolic pressure > 110 mmHg).

          -  No known hypersensitivity to mammalian cell-derived products or human albumin.

          -  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.

          -  Females of childbearing potential and males must be willing to use an effective method
             of contraception (hormonal or barrier method of birth control; abstinence) while on
             treatment and for a 4-week period thereafter.

          -  Females with childbearing potential must have a negative pregnancy test within 7 days
             prior to being randomized. Patients are considered not of child bearing potential if
             they are surgically sterile (they have undergone a hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or they are postmenopausal.