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Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
This study has been terminated.
( Please see detailed description under Purpose )

First Received on January 31, 2008.   Last Updated on December 15, 2011   History of Changes
Sponsor: Amgen
Information provided by: Amgen
ClinicalTrials.gov Identifier: NCT00614523
  Purpose

The DMC for study 20060198, based on review of interim data, recommended modification of study conduct. The DMC expressed their concern that the potential benefit seen in the reduction of bleeding events did not outweigh the potential risk that transient increases in blast cell counts in the romiplostim arm put subjects at risk for diagnosis of and treatment for AML.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
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)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Number of clinically significant bleeding events [ Time Frame: Test Treatment Period (Week 1-26) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of platelet transfusion events [ Time Frame: Test Treatment Period (Week 1-26) ] [ Designated as safety issue: No ]
  • Number of overall bleeding events [ Time Frame: Test Treatment Period (Week 1-26) ] [ Designated as safety issue: No ]
  • Number of units of platelets transfused [ Time Frame: Test Treatment Period (Week 1-26) ] [ Designated as safety issue: No ]
  • Number of subjects with platelet hematologic improvement (HI-P) per MDS IWG 2006 guidelines [ Time Frame: Test Treatment Period (W1-26) ] [ Designated as safety issue: No ]
  • Duration of platelet hematologic improvement (HI-P) in the absence of platelet transfusions per MDS IWG 2006 guidelines [ Time Frame: Test Treatment Period (Week 1-26) ] [ Designated as safety issue: No ]
  • Time to death [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]
  • Number of patient-reported bleeding events [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]

Enrollment: 250
Study Start Date: May 2008
Estimated Study Completion Date: March 2016
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Romiplostim 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 Comparator: Placebo 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.

Detailed Description:

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 4 week interim wash-out period, a 24-week placebo controlled extended treatment period, and a 4-week follow-up period followed by an End of Study (EOS) visit. 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.

  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 for myeloid neoplasms as assessed during the screening period.
  • Per MDS IPSS, low or intermediate-1 risk MDS as assessed during the screening period.
  • 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 during the screening period), with or without a history of bleeding associated with the diagnosis of MDS, OR
    • ≤ 50 x 10^9/L, (with no individual count >60 x 10^9/L during the screening period) with a history of bleeding associated with the diagnosis of MDS.
  • 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 ALT ≤ 3 times the laboratory normal range, AST ≤ 3 times the laboratory normal range and total bilirubin ≤ 2.0 times the laboratory normal range.

(Adequate liver function for patients with a confirmed diagnosis of Gilbert's Disease evidenced by 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) or known diagnosis of Chronic Myelomonocytic Leukemia per FAB criteria.
  • 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.
  • Subject has known sensitivity to any recombinant E coli-derived product (eg, Infergen®, Neupogen®, Somatropin, and Actimmune).
  • Previously enrolled into the 20060198 study or another romiplostim study.
  • Inability 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00614523

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

Additional Information:
No publications provided

Responsible Party: Global Development Leader, Amgen Inc.
ClinicalTrials.gov Identifier: NCT00614523     History of Changes
Other Study ID Numbers: 20060198
Study First Received: January 31, 2008
Last Updated: December 15, 2011
Health Authority: 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: 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;   Austria: Federal Ministry for Health and Women;   Denmark: Danish Medicines Agency;   Denmark: Laegemiddelstyrelsen;   Denmark: Ministry of Health;   EU: CHMP;   European Union: European Medicines Agency;   France and Sweden: European Medicines Agency;   France: Afssaps - French Health Products Safety Agency;   France: CCPPRB Central Ethics Committee;   France: Ministry of Health;   Germany: Federal Institute for Drugs and Medical Devices;   Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe;   Hungary: National Institute of Pharmacy;   Ireland: Irish Medicines Board;   Italy: Local Ethics Committees;   Italy: Ministry of Health;   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;   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;   Switzerland: Agency for Therapeutic Products;   Switzerland: Local Ethics Committee;   Switzerland: Swissmedic (Swiss Agency for Therapeutic Products);   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);   United Kingdom: Medicines and Healthcare Products Regulatory Agency;   United States: Food and Drug Administration;   United States: Western Institutional Review Board

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

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

ClinicalTrials.gov processed this record on February 09, 2012