Determination of Safe Dose of Romiplostim (AMG 531) in Patients With Myelodysplastic Syndromes (MDS)

• Status: Completed
• Trial end date: 2008-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amgen

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