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Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
This study is currently recruiting participants.
Verified by Amgen, January 2009
Sponsored by: Amgen
Information provided by: Amgen
ClinicalTrials.gov Identifier: NCT00614523
  Purpose

This is a Phase 2, multicenter, randomized, double blind, placebo controlled study designed to assess the efficacy and safety of romiplostim (formerly, AMG 531) treatment in thrombocytopenic MDS subjects. The study is composed of a 26-week placebo controlled test treatment period (romiplostim versus Placebo), a 2 to 4 week interim wash-out period, a 24-week placebo controlled extended treatment period, and a 4-week follow-up period. During the interim wash-out period, a bone marrow biopsy will be performed in the absence of growth factor to assess changes in the marrow. In the extended treatment period, safety assessments will continue and subjects will be allowed to receive any standard of care treatments for MDS.

Subjects will be followed for survival for an additional 60 months following the End of Study (EOS) visit.


Condition Intervention Phase
MDS
Myelodysplastic Syndromes
Thrombocytopenia
Biological: Romiplostim
Drug: Placebo
Phase II

Drug Information available for: Amphetamine Methamphetamine
U.S. FDA Resources
Study Type: Interventional
Study Design: Supportive Care, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title: A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Further study details as provided by Amgen:

Primary Outcome Measures:
  • To evaluate the efficacy of romiplostim for the treatment of thrombocytopenia in subjects with international prognostic scoring system (IPSS) low or intermediate-1 risk MDS as measured by the number of clinically significant bleeding events. [ Time Frame: Test Treatment Period (W1-26) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the number of platelet transfusions [ Time Frame: Test Treatment Period (W1-26) ] [ Designated as safety issue: No ]
  • To evaluate the overall number of bleeding events [ Time Frame: Test Treatment Period (W1-26) ] [ Designated as safety issue: No ]
  • To evaluate the utilization of platelet transfusions [ Time Frame: Test Treatment Period (W1-26) ] [ Designated as safety issue: No ]
  • To evaluate platelet hematologic improvement (HI-P), per MDS IWG 2006 guidelines [ Time Frame: Test Treatment Period (W1-26) ] [ Designated as safety issue: No ]
  • To evaluate overall survival [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]
  • To evaluate patient-reported bleeding events [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]
  • The incidence and severity of all adverse events including clinically significant changes in laboratory values [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • The incidence of disease progression to acute myelogenous leukemia (AML) [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • The incidence of neutralizing romiplostim antibody formation and antibodies that crossreact react with eTPO [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 240
Study Start Date: May 2008
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Romiplostim: Experimental Biological: Romiplostim
Weekly subcutaneous dosing based on platelet count. Starting dose is at 750mcg, up to a maximum dose of 1000mcg, or reduced to a minimum of 250mcg . Romiplostim is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.
Placebo: Placebo Comparator Drug: Placebo
Weekly subcutaneous dosing based on platelet count. Starting dose is at 750mcg, up to a maximum dose of 1000mcg, or reduced to a minimum of 250mcg. Placebo is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of MDS using the WHO classification
  • Per MDS IPSS, low or intermediate-1 risk MDS
  • The mean of the two platelet counts taken within 4 weeks prior to randomization must be:

    • ≤ 20 x 10^9/L, with no individual count >30 x 10^9/L, with or without a history of bleeding, OR
    • ≤ 50 x 10^9/L, with no individual count >60 x 10^9/L with a history of clinically significant bleeding.
  • Subjects must be ≥18 and ≤ 90 years of age at the time of informed consent. Subjects between 85 and 90 years of age must have been diagnosed with MDS ≤ 5 years from study start.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate liver function, as evidenced by a serum bilirubin ≤ 2 times the laboratory normal range and unconjugated bilirubin ≥ 90% of total bilirubin (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 μmol/L)
  • Bone marrow biopsy and aspirate with cytogenetics within 3 months of starting first dose of investigational product
  • Written Informed Consent

Exclusion Criteria:

  • Have ever received any disease-modifying treatment for MDS
  • Previously diagnosed with intermediate-2 or high risk MDS using the IPSS
  • Prior history of leukemia, aplastic anemia, or other non-MDS related bone marrow stem cell disorder
  • Prior history of hematopoietic stem cell transplantation
  • Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count >1,000/μL)
  • Prior malignancy (other than in situ cervical cancer, non-melanoma skin cancer, or in situ carcinoma) unless treated with curative intent and without evidence of disease for ≥ 3 years before randomization
  • Active or uncontrolled infections
  • Unstable angina, congestive heart failure (NYHA > class II), uncontrolled hypertension (diastolic >100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
  • History of arterial thrombosis (eg, stroke or transient ischemic attack) within the past year
  • History of venous thrombosis that currently requires anti-coagulation therapy
  • Received IL-11 within 4 weeks of the first dose of investigational product
  • Have previously received any thrombopoietic growth factor
  • Receipt of G-CSF, peg-G-CSF, or GM-CSF within 4 weeks of the first dose of investigational product
  • Planned receipt of peg-G-CSF or GM-CSF after the first dose of investigational product
  • Pregnant or breast feeding
  • Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. Amgen recommends double barrier contraception is used for all applicable patients enrolled on this study. A double barrier method is defined as two methods of contraception, for example 2 actual barrier methods, or one actual barrier method and one hormonal method.
  • Known hypersensitivity to any recombinant E coli-derived product (eg, Infergen®, Neupogen®, Somatropin, and Actimmune)
  • Previously enrolled in this study
  • Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
  • Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00614523

Contacts
Contact: Amgen Call Center 866-572-6436

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

AmgenTrials clinical trials website  This link exits the ClinicalTrials.gov site

Responsible Party: Amgen Inc. ( Global Development Leader )
Study ID Numbers: 20060198
Study First Received: January 31, 2008
Last Updated: January 6, 2009
ClinicalTrials.gov Identifier: NCT00614523  
Health Authority: Austria: Secretariat of Health;   Belgium: Directorate general for the protection of Public health: Medicines;   Belgium: Directorate-General for Medicinal Products;   Belgium: Federal Public Service (FPS) Health, Food Chain Safety and Environment;   Belgium: FPS of Public Health, Food Chain Security and Environment;   Belgium: Pharmaceutical Inspectorate;   Belgium: Service Public Federal Sante Publiquest, Securite de la Chaine alimentaire et Environnement;   Belgium: Service Public Fédéral Santé Publique, Sécurité de la Chaîne alimentaire et Environnement;   Canada: Health Canada;   Canada: Health Products and Food Branch;   Canada: Institutional Review Board;   Czech Republic: State Institute for Drug Control;   Czech Republic: Statni ustav pro kontrolu leciv;   Denmark: Central Ethics Committee;   Denmark: Danish Medicines Agency;   Denmark: Laegemiddelstyrelsen;   Australia: Department of Health and Ageing Therapeutic Goods Administration;   Australia: Human Research Ethics Committee;   Australia: Therapeutic Goods Administration;   Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information;   Austria: Bundesamt fur Sicherheit im Gesundheitswesen;   Austria: Bundesamt für Sicherheit im Gesundheitswesen;   Austria: Central Ethics Committee;   Austria: Competant Authority;   Austria: Federal Ministry for Health and Women;   Denmark: Ministry of Health;   Estonia: State Agency of Medicines;   EU: CHMP;   European Union: European Medicines Agency;   France and Sweden: European Medicines Agency;   France: Ministry of Health;   Germany: Federal Institute for Drugs and Medical Devices;   Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe;   France: Afssaps - French Health Products Safety Agency;   France: CCPPRB Central Ethics Committee;   Hungary: National Institute of Pharmacy;   Ireland: Irish Medicines Board;   Italy: Local Ethics Committees;   Italy: Ministry of Health;   Latvia: State Agency of Medicines;   Lithuania: Ministry of Health;   Lithuania: State Medicines Control Agency of Lithuania;   Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research;   Netherlands: Medicines Evaluation Board;   Netherlands: Medisch Centrum Rijnmond_Zuid, lcatie Zuider;   Norway: Norwegian Medicines Agency;   Poland: Drug Institut;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Portugal: Instituto Nacional da Farmácia e do Medicamento (INFARMED);   Portugal: National Institute of Pharmacy and Medicines;   Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health);   Russia: Ministry of Health;   Slovakia: Ministry of Health;   Slovakia: State Institiute for Drug Control;   Slovakia: Štátny ústav pre kontrolu lieciv;   Spain: Agencia Española de Medicamentos y Productos Sanitarios;   Spain: Spanish Agency of Medicines;   Spain: Spanish Drug Agency;   Sweden: Central Ethics Committee;   Sweden: Lakemedelsverket;   Sweden: Medical Products Agency;   United Kingdom: Medicines and Healthcare Products Regulatory Agency;   United States: Food and Drug Administration

Keywords provided by Amgen:
MDS
Low Risk MDS
Intermediate-1 Risk MDS
Thrombocytopenia

Study placed in the following topic categories:
Myelodysplastic syndromes
Thrombocytopathy
Methamphetamine
Preleukemia
Thrombocytopenia
Precancerous Conditions
Hematologic Diseases
Blood Platelet Disorders
Myelodysplasia
Myelodysplastic Syndromes
Amphetamine
Bone Marrow Diseases

Additional relevant MeSH terms:
Neoplasms
Pathologic Processes
Disease
Syndrome

ClinicalTrials.gov processed this record on January 16, 2009