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An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Conditions
ow or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Registration Number
EUCTR2006-000144-92-NL
Lead Sponsor
Amgen Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
55
Inclusion Criteria

Diagnosis of MDS using the World Health Organization classification
Low or intermediate-1 risk MDS using the IPSS
The mean of the two platelet counts taken within 1 week prior to dosing must be =50 x 109/L, with no individual count >55 x 109/L (5 patients enrolled at the MTD must be =20 x 109/L)
Subjects must be 18 years of age at the time of obtaining informed consent
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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 (=176.8 mmol/L)
Written Informed Consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Currently receiving any treatment for MDS other than supportive care
Clinically significant bleeding within 2 weeks of screening (ie: 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
History of coronary artery disease, congestive heart failure, uncontrolled angina or a recent (within 1 year) myocardial infarction
Known history of thromboembolic disease
Untreated B12 or folate deficiency
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
Concurrent use of granulocyte growth factors
Received IL-11 (oprelvekin) within 4 weeks of screening
Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication
Have ever previously received rTPO, PEG-rHuMGDF, eltrombopag, or AMG 531
Pregnant or breast feeding
Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
Known hypersensitivity to any recombinant E coli-derived product
Previously enrolled in this study
Will not be available for follow-up assessment
Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate the safety and tolerability of AMG 531 in thrombocytopenic subjects with low or Intermediate-1 risk MDS.;Secondary Objective: To evaluate the platelet response of thrombocytopenic subjects with low or intermediate-1 risk MDS receiving AMG 531.;Primary end point(s): The primary endpoint is the incidence and severity of all adverse events and evaluation of antibody status. The MTD of AMG 531 in thrombocytopenic subjects with low or intermediate-1 risk MDS will be identified based on safety data. The MTD is defined as the dose where < 34% of subjects experience a related grade 3-4 toxicity. The key secondary endpoint is the proportion of subjects achieving a complete or major platelet response (platelet response defined by a modified MDS International Working Group Classification).
Secondary Outcome Measures
NameTimeMethod
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