Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Condition: MDS; Myelodysplastic Syndromes; Thrombocytopenia
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Thrombocytopenia; Syndrome
Intervention: Placebo; Romiplostim
Intervention description: Placebo is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.; Romiplostim is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 250.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: MDS; Low Risk MDS; Intermediate-1 Risk MDS; Thrombocytopenia

Summary:

      The Data Monitoring Committee (DMC) for study 20060198 recommended that all subjects
      discontinue treatment of study drug and continue to be followed for long term follow-up.
      Amgen adopted the DMC recommendation.
    

Eligibility criteria:

        Inclusion Criteria: • Diagnosis of MDS using the World Health Organization (WHO)
        classification for myeloid neoplasms as assessed during the screening period. • Per MDS
        International Prognostic Scoring System (IPSS), low or intermediate-1 risk MDS as assessed
        during the screening period. • Mean of the 2 platelet counts taken within 4 weeks prior to
        randomization must be: - ≤ 20 x 10^9/L, (with no individual count >30 x 10^9/L during the
        screening period), with or without history of bleeding associated with diagnosis of MDS, OR
        - ≤ 50 x 10^9/L, (with no individual count >60 x 10^9/L during the screening period) with a
        history of bleeding associated with the diagnosis of MDS. • Patients must be ≥18 and ≤ 90
        years of age at time of informed consent. Patients between 85 and 90 years of age must have
        been diagnosed with MDS ≤ 5 years from study start. • Eastern Cooperative Oncology Group
        (ECOG) performance status of 0-2. • Adequate liver function, as evidenced by alanine
        aminotransferase (ALT) ≤ 3 times laboratory normal range, aspartate aminotransferase (AST)
        ≤ 3 times laboratory normal range and total bilirubin ≤ 2.0 times laboratory normal range.
        (Adequate liver function for patients with confirmed diagnosis of Gilbert's Disease
        evidenced by ALT ≤ 3 times laboratory normal range, and AST ≤ 3 times laboratory normal
        range.) • Serum creatinine concentration ≤ 2 mg/dl (≤176.8 μmol/L). • Bone marrow biopsy
        and aspirate with cytogenetics within 3 months of starting first dose of investigational
        product. • Written Informed Consent. Exclusion Criteria: • Have ever received any
        disease-modifying treatment for MDS. • Previously diagnosed with intermediate-2 or high
        risk MDS using the IPSS. • Prior history of leukemia, aplastic anemia, or other non-MDS
        related bone marrow stem cell disorder. • Prior history of hematopoietic stem cell
        transplantation. • Persistent peripheral blood monocytosis (≥ 3 months with an absolute
        monocyte count >1,000/μL) or known diagnosis of Chronic Myelomonocytic Leukemia per
        French-American-British Classification System for MDS (FAB) criteria. • Prior malignancy
        (other than in situ cervical cancer, non-melanoma skin cancer, or in situ carcinoma) unless
        treated with curative intent and without evidence of disease for ≥ 3 years before
        randomization. • Active or uncontrolled infections. • Unstable angina, congestive heart
        failure (New York Heart Association [NYHA] > 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) within the past year. • History of venous thrombosis that currently requires
        anti-coagulation therapy. • Received Interleukin (IL)-11 within 4 weeks of first dose of
        investigational product. • Have previously received any thrombopoietic growth factor. •
        Receipt of granulocyte-colony stimulating factor, (G-CSF), pegylated-G-CSF, or granulocyte
        macrophage-colony stimulating factor (GM-CSF) within 4 weeks of first dose of
        investigational product. • Planned receipt of peg-G-CSF or GM-CSF after first dose of
        investigational product. • Pregnant or breast feeding. • Patients of reproductive potential
        who are not using adequate contraceptive precautions, in the judgment of the investigator.
        Amgen recommends double barrier contraception is used for all applicable patients enrolled
        on this study. A double barrier method is defined as two methods of contraception, for
        example 2 actual barrier methods, or one actual barrier method and one hormonal method. •
        Patient has known sensitivity to any recombinant E coli-derived product (eg, Infergen®,
        Neupogen®, Somatropin, and Actimmune). • Previously enrolled into the 20060198 study or
        another romiplostim study. • Inability to comply with study procedures. • Patient currently
        is enrolled in or has not yet completed at least 30 days since ending other investigational
        device or drug study.