A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Azacitidine; Physician Choice
Intervention description: Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m^2/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.; Physician Choice was one of three options:
Best supportive care (BSC) alone,
Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or
Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle).
All three options included best supportive care
Intervention MeSH terms: Cytarabine; Azacitidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 358.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether patients with high-risk myelodysplastic
      syndromes (MDS) treated with azacitidine have improved survival compared to conventional care
      treatments. The study will also assess the effect of treatments on response, duration of
      response, and transformation to acute myeloid leukemia (AML). The study will continue for 12
      months following last patient enrolled.

      See study AZA PH GL 2003 CL 001 E for information about the extension to this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of refractory anemia with excess blasts or refractory anemia with
             excess blasts in transformation according to the French-American-British
             classification system for myelodysplastic syndromes (MDS) and a relatively high risk
             of acute myeloid leukemia (AML) transformation, with an International Prognostic
             Scoring System score of INT-2 or High.

          -  Be 18 years of age or older

          -  Have a life expectancy of at least 3 months

          -  Be unlikely to proceed to bone marrow or stem cell transplantation therapy following
             remission

          -  Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal
             range for the laboratory

          -  Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum
             glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to
             2 times the upper limit of normal (unless these are considered to be related to
             transfusion-induced secondary hemosiderosis)

          -  Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal

        Exclusion Criteria:

          -  Secondary myelodysplastic syndromes (MDS)

          -  Prior treatment with azacitidine;

          -  Prior history of acute myeloid leukemia (AML);

          -  Malignant disease diagnosed within prior 12 months;

          -  Metastatic disease;

          -  Hepatic tumors;

          -  Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12
             months;

          -  Prior transplantation or cytotoxic therapy to treat MDS;

          -  Serious medical illness likely to limit survival to 12 months or less;

          -  Treatment with erythropoietin or myeloid growth factors during prior 21 days or
             androgenic hormones during prior 13 days;

          -  Active HIV, viral hepatitis type B or C;

          -  Treatment with investigational drugs during prior 30 days;

          -  Within the 28-day screening period, documented red cell folate deficiency, as
             evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency