The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)
Condition: Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Thrombocytopenia; Syndrome
Intervention: Oral Azacitidine; Placebo; Best Supportiv Care (BSC)
Intervention description: 300 mg daily, days 1 to 21 of each 28-day treatment cycle; Identically matching placebo tablets on day 1 to 21 of each 28-day treatment cycle.; BSC included and was not limited to packed RBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Intervention MeSH terms: Azacitidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 216.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus
      Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent
      anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk
      myelodysplastic syndromes (MDS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years or older

          -  Have a documented diagnosis of MDS

          -  Anemia that requires red blood cell transfusions

          -  Thrombocytopenia (sustained for at least 21 days) within 14 days prior to
             randomization

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Must agree to follow pregnancy precautions as required by protocol.

          -  Understand and voluntarily sign an informed consent document prior to any study
             related assessments/procedures being conducted

        Exclusion Criteria:

          -  Secondary or hypoplastic MDS or other subtype with eligibility for treatment with
             immunotherapy

          -  Prior treatment with azacitidine, decitabine, other hypomethylating agents and
             lenalidomide (for lenalidomide : unless the last dose received is >= 8 weeks prior to
             inclusion into the study).

          -  Prior allogeneic or autologous stem cell transplant

          -  Eligible for allogenic or autologous stem cell transplant

          -  History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis),
             celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other
             gastrointestinal disorder or defect

          -  Thrombocytopenia secondary to other possible causes, including medication(s),
             congenital disorder(s), immune disorder(s), or microvascular disorder(s)

          -  Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies,
             thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and
             other red blood cell hematopoietic growth factors, and within 28 days prior to
             randomization

          -  Ongoing medically significant adverse events from previous treatment, regardless of
             the time period

          -  Concurrent use of iron-chelating agents, (except for subjects on a stable or
             decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid
             (except for subjects on a stable or decreasing dose for ≥ 1 week prior to
             randomization for medical conditions other than MDS)

          -  Prior history of cancer, other than MDS, unless the subject has been free of the
             disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in
             situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding
             of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical
             staging system is allowed)

          -  Significant active cardiac disease within the previous 6 months

          -  Uncontrolled systemic fungal, bacterial, or viral infection

          -  Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence
             of active Hepatitis B Virus (HBV) infection

          -  Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies,
             or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding

          -  Abnormal coagulation parameters

          -  Abnormal liver function test results

          -  Abnormal kidney function test results

          -  Known or suspected hypersensitivity to azacitidine or mannitol

          -  Any significant medical condition, laboratory abnormality, or psychiatric illness