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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00472290
First received: May 10, 2007
Last updated: September 18, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Hematology
MDS
Myelodysplastic Syndromes
Thrombocytopenia
Drug: Romiplostim (formerly AMG 531)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Extension Study Evaluating the Safety of Long Term Dosing of Romiplostim in Thrombocytopenic Subjects With Myelodysplastic Syndromes (MDS)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Overall Summary of Adverse Events [ Time Frame: During treatment period from first dose of IP to End of Study visit, on Average 56 Weeks . ] [ Designated as safety issue: Yes ]
  • Incidence of Antibody (AB) Formation [ Time Frame: During treatment period from first dose of IP to End of Study visit, on Average 56 Weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Weekly Bleeding Events Per 100 Subject Years [ Time Frame: During the treatment period. The average duration of romiplostim exposure is 56 weeks. ] [ Designated as safety issue: No ]
    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.

  • Platelet Transfusion Events Per 100 Subject Years [ Time Frame: During the treatment period. The average duration of romiplostim exposure is 56 weeks. ] [ Designated as safety issue: No ]
    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.

  • Weeks With Platelet Response Per Year [ Time Frame: During the treatment period. The average duration of romiplostim exposure is 56 weeks. ] [ Designated as safety issue: No ]
    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.

  • Time to First Platelet Response [ Time Frame: During treatment period. The average duration of romiplostim exposure is 56 weeks. ] [ Designated as safety issue: No ]
    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.

  • Duration of Platelet Response [ Time Frame: During treatment period. The average duration of romiplostim exposure is 56 weeks. ] [ Designated as safety issue: No ]
    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.


Enrollment: 72
Study Start Date: April 2007
Study Completion Date: December 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label Romiplostim (formerly AMG 531) Drug: Romiplostim (formerly AMG 531)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00472290

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00472290     History of Changes
Other Study ID Numbers: 20060197
Study First Received: May 10, 2007
Results First Received: December 5, 2012
Last Updated: September 18, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
Czech Republic: Local Ethics Committees for each involved site ( 6 Local EC)
Czech Republic: Multicentrics Ethics Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Central EC, called Comite de Protection des Personnes
France: CNIL: National Computers and Privacy Commission
France:CNOM: National Council of the French Medical Association
Germany: Bundesinstitut fur Arzneimittel und Medizinprodukte
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Ireland: Main Ethics Committee
Italy: Local Ethics Committees
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Poland: Central Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health)
Russia: Ministry of Health
Russia: National Ethic Committee
Austria: Bundesamt fur Sicherheit im Gesundheitswesen
Austria: Central Ethics Committee
Slovakia: Ministry of Health
Slovakia: State Institiute for Drug Control
Slovakia: Štátny ústav pre kontrolu lieciv
Spain: Comité ético del Hospital Vall d'Hebron
Spain: reference Ethics Committee
Spain: Spanish Agency of Medicines
Spain: Spanish Drug Agency
Sweden: Medical Products Agency
Switzerland: Local Ethics Committee
Switzerland: Swissmedic (Swiss Agency for Therapeutic Products)
United Kingdom: Main Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Amgen:
Hematology
MDS
Myelodysplastic Syndromes
Thrombocytopenia

Additional relevant MeSH terms:
Thrombocytopenia
Myelodysplastic Syndromes
Preleukemia
Syndrome
Blood Platelet Disorders
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes

ClinicalTrials.gov processed this record on September 16, 2014