Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents
Condition: MDS; Myelodysplastic Syndromes; Thrombocytopenia
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Thrombocytopenia; Syndrome
Intervention: Placebo; AMG 531 (Romiplostim); Azacitidine; Decitabine
Intervention description: Subjects in the control group will receive a placebo subcutaneous injection on a weekly basis during the 4 cycle treatment period.; AMG 531 (Romiplostim) will be administered weekly by subcutaneous injection at a dose of 500 or 750 μg during Part A and 750 μg during Part B for the 4 cycle treatment period, depending on randomization.; hypomethylating agent; hypomethylating agent
Intervention MeSH terms: Azacitidine; Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDS; Myelodysplastic Syndromes; Refractory Cytopenias; Thrombocytopenia

Summary:

      The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence
      of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet
      transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS)
      receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the
      appropriate dose and schedule, will result in reduction in the incidence of clinically
      significant thrombocytopenic events in low or intermediate risk MDS subjects receiving
      hypomethylating agents.
    

Eligibility criteria:

        Inclusion Criteria: - Diagnosis of MDS by bone marrow biopsy based on the World Health
        Organization (WHO) classification - Low, Intermediate-1 or Intermediate-2 risk category MDS
        using the IPSS (International Prognostic Scoring System) - Planned to receive either
        azacytidine 75 mg/m2 by subcutaneous administration each day for 7 days or decitabine 20
        mg/m2 by intravenous administration each day for 5 days for at least 4 cycles Exclusion
        Criteria:

          -  Prior exposure to >3 cycles hypomethylating agents

          -  Prior history of leukemia or aplastic anemia

          -  Prior history of bone marrow transplantation

          -  Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin)
             unless treated with curative intent and without evidence of disease for ³ 3 years
             before randomization

          -  Active or uncontrolled infections

          -  Unstable angina, congestive heart failure [NYHA (New York Heart Association) > class
             II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac
             arrhythmia, or recent (within 1 year) myocardial infarction

          -  History of arterial thrombosis ( eg, stroke or transient ischemic attack) in the past
             year

          -  History of venous thrombosis that currently requires anti-coagulation therapy

          -  Received IL-11 within 4 weeks of screening

          -  Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA
             approved for any indication

          -  Have previously received any other thrombopoietic growth factor