determination of safe dose of romiplostim (amg 531) in patients with myelodysplastic syndromes (mds)

Conditions: Thrombocytopenia; MDS; Myelodysplastic Syndromes; Refractory Cytopenias

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

Keywords: mds myelodysplastic syndromes refractory cytopenias thrombocytopenia