Evaluating the Safety of Long Term Dosing of Romiplostim (Formerly AMG 531) in Thrombocytopenic Subjects With Myelodysplastic Syndromes (MDS)

Study Overview
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Brief Summary
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This is an open label extension study of romiplostim for treatment of thrombocytopenia (platelet count ≤ 50 x 10^9/L) in MDS subjects. The study is designed to assess the long-term safety of treatment with romiplostim, as measured by incidence of overall adverse events, the incidence of bleeding events, the utilization of platelet transfusions, and the duration of platelet response. The study will further describe the time to disease progression to acute myeloid leukemia (AML) and survival.

Official Title
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An Open Label Extension Study Evaluating the Safety of Long Term Dosing of Romiplostim in Thrombocytopenic Subjects With Myelodysplastic Syndromes (MDS)

Conditions
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Hematology, MDS, Myelodysplastic Syndromes, Thrombocytopenia

Intervention / Treatment
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* Drug: Romiplostim (formerly AMG 531)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject completed a romiplostim study for the treatment of thrombocytopenia in subjects with MDS Subject has an Eastern Cooperative Oncology (ECOG) performance status of 0 to 2 Subject had a platelet count ≤ 50 x 10^9/L since the final dose of investigational product in the parent study Subject or his/her legally acceptable representative provided written informed consent before any study-specific procedures were initiated Exclusion Criteria Subject has been diagnosed with AML or has a blast count ≥ 10% by peripheral blood or bone marrow biopsy Subject has a prior history of leukemia Subject has a prior history of bone marrow or stem cell transplantation Subject has a prior malignancy (other than in situ cervical cancer, controlled prostate cancer, or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years before randomization Subject has active or uncontrolled infections Subject has 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 Subject has a history of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year Subject has a history of venous thrombosis that currently requires anti-coagulation therapy Subject received interleukin (IL)-11 within 4 weeks of screening Subject previously received a thrombopoietic growth factor (other than romiplostim) Subject has a known hypersensitivity to any recombinant E coli-derived product (eg, Infergen®, Neupogen®, Somatropin, Actimmune) Subject is currently enrolled in investigational device or drug study(ies), has not yet completed at least 4 weeks since ending investigational device or drug study(ies) (other than parent romiplostim study), or subject is receiving other investigational agent(s)/device(s) Subject is of child-bearing potential and is evidently pregnant (eg, positive human chorionic gonadotropin [HCG] test) or is breast feeding Subject is not using adequate contraceptive precautions Subject has any kind of disorder that compromises his/her ability to give written informed consent (and does not have a legally acceptable representative) or is unable to comply with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label Romiplostim (formerly AMG 531)<br> | Drug: Romiplostim (formerly AMG 531)<br>* Subjects will begin the study at an initial dose of 750 µg. Except for: Subject whose doses were escalated to doses higher than 750 µg AMG 531 weekly, and maintained a response per IWG guidelines for platelet response. Subjects who were stable at a lower dose of AMG 531 on the previous study. Doses will be adjusted throughout the study based on individual subject's platelet count.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Summary of Adverse Events |  | During treatment period from first dose of IP to End of Study visit, on Average 56 Weeks . | 
| Incidence of Antibody (AB) Formation |  | During treatment period from first dose of IP to End of Study visit, on Average 56 Weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Bleeding Events Per 100 Subject Years | During the time since the first dose of IP to the end of the treatment period. A single bleeding event was defined as each individual bleeding episode that originated from a specific organ system (eg, gastrointestinal system or central nervous system). A bleeding event that continued for more than 7 days was counted as separate events every eighth day. | During the treatment period. The average duration of romiplostim exposure is 56 weeks. | 
| Platelet Transfusion Events Per 100 Subject Years | During the time since the first dose of IP to the end of the treatment period. A discrete platelet transfusion event was defined as any number of platelet transfusions administered within a 3-day period. Platelet transfusions administered more than 3 days apart were counted as separate platelet transfusion events. | During the treatment period. The average duration of romiplostim exposure is 56 weeks. | 
| Weeks With Platelet Response Per Year | During the time since the first dose of IP to the end of the treatment period. Platelet response was based on the modified IWG 2006 criteria (Cheson et al, 2006) and was defined as, in the absence of platelet transfusion: an absolute increase in platelet count of ≥ 30 x 10^9/L for a subject starting with a platelet count of ≥ 20 x 10^9/L; or an increase in platelet count from < 20 x 10^9/L to ≥ 20 x 10^9/L and by at least 100% in a subject that started with a platelet count < 20 x 10^9/L. | During the treatment period. The average duration of romiplostim exposure is 56 weeks. | 
| Time to First Platelet Response | Time since first dose of IP to the first platelet response. Platelet response was based on the modified IWG 2006 criteria (Cheson et al, 2006) and was defined as, in the absence of platelet transfusion: an absolute increase in platelet count of ≥ 30 x 10^9/L for a subject starting with a platelet count of ≥ 20 x 10^9/L; or an increase in platelet count from < 20 x 10^9/L to ≥ 20 x 10^9/L and by at least 100% in a subject that started with a platelet count < 20 x 10^9/L. | During treatment period. The average duration of romiplostim exposure is 56 weeks. | 
| Duration of Platelet Response | Platelet response was based on the modified IWG 2006 criteria (Cheson et al, 2006) and was defined as, in the absence of platelet transfusion: an absolute increase in platelet count of ≥ 30 x 10^9/L for a subject starting with a platelet count of ≥ 20 x 10^9/L; or an increase in platelet count from < 20 x 10^9/L to ≥ 20 x 10^9/L and by at least 100% in a subject that started with a platelet count < 20 x 10^9/L. | During treatment period. The average duration of romiplostim exposure is 56 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematology, MDS, Myelodysplastic Syndromes, Thrombocytopenia