Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)
Condition: Thrombocytopenia; MDS; Myelodysplastic Syndromes; Refractory Cytopenias
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Thrombocytopenia; Syndrome
Intervention: Romiplostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 72.0
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 safety and tolerability of romiplostim in
      thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will
      evaluate the platelet response to romiplostim.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of MDS using the World Health Organization classification

          -  Low or Intermediate-1 risk MDS using the International Prognostic Scoring System
             (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 maximum tolerated dose (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.

          -  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),
             alanine aminotransferase (ALT) ≤ 3 times the laboratory normal range, and aspartate
             aminotransferase (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,
             gastrointestinal (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 (New York Heart Association [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 interleukin (IL)-11 (oprelvekin) within 4 weeks before screening

          -  Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating
             factor [G-CSF; Neupogen, Granocyte], pegfilgrastim [Neulasta], granulocyte
             macrophage-colony stimulating factor [GM-CSF; Leukine, Prokine, Sargramostim])

          -  Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant
             human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or
             romiplostim

          -  Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and
             Drug Administration (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 human chorionic gonadotropin [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