Determination of Safe Dose of Romiplostim (Formerly AMG 531) in Subjects With MDS

Inclusion Criteria:

• Diagnosis of MDS using the World Health Organization classification
• Low or Intermediate-1 risk MDS using the IPSS
• The mean of two platelet counts taken during the screening period must be ≤ 50 x 10^9/L, with no individual count > 55 x 10^9/L (The mean platelet counts of 5 subjects enrolled at the MTD must be ≤ 20 x 10^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1.
• Subjects must be ≥ 18 years of age at the time of obtaining informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening
• Adequate Liver Function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), ALT ≤ 3 times the laboratory normal range, and AST ≤ 3 times the laboratory normal range
• A serum creatinine concentration ≤ 2 mg/dL (≤ 176.6 µmol/L)
• Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1)

Exclusion Criteria:

• Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1
• Clinically significant bleeding within 2 weeks prior to screening (eg, GI bleeds, intracranial hemorrhage)
• Prior malignancy (other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years before screening
• Prior history of bone marrow transplantation
• Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count > 1,000/µL)
• Unstable angina, congestive heart failure [NYHA > class II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
• Received Anti-Thymocyte Globuline (ATG) within 6 months of screening
• Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening
• Received IL-11 (oprelvekin) within 4 weeks before screening
• Concurrent use of granulocyte growth factors (i.e. G-CSF(Neupogen, Granocyte), pegfilgrastim (Neulasta), GM-CSF (Leukine, Prokine, Sargramostim))
• Have ever previously received rTPO, PEG-rHuMGDF, eltrombopag, or romiplostim
• Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication
• Other investigational procedures are excluded
• History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year
• History of venous thrombosis that currently requires anti-coagulation therapy
• Untreated B12 or folate deficiency
• Subject is evidently pregnant (eg, positive HCG test) or is breast feeding
• Subject is not using adequate contraceptive precautions
• Subject has known hypersensitivity to any recombinant E coli-derived product
• Subject previously has enrolled in this study
• Subject will not be available for follow-up assessment
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures