Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With ITP

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00907478
First received: May 21, 2009
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This is a prospective, phase IV, multi-center, open label, study evaluating the changes in bone marrow reticulin and collagen in adult subjects receiving romiplostim for the treatment of thrombocytopenia associated with ITP.


Condition Intervention Phase
Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
Biological: romiplostim
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Phase IV, Open-Label, Multi-Center Study Evaluating Changes in Bone Marrow Morphology in Adult Subjects Receiving Romiplostim for the Treatment of Thrombocytopenia Associated With Immune (Idiopathic) Thrombocytopenia Purpura (ITP)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • The incidence of collagen fibrosis as evidenced by trichrome staining [ Time Frame: At Years 1, 2 or 3 after initial exposure of romiplostim ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The incidence of clinically relevant changes in QT/QTc intervals, as defined as an absolute QTc interval > 500 ms or a QTc interval increase from baseline ≥ 60 ms post romiplostim exposure [ Time Frame: from Week 3 through End of Study (maximum total time is approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
  • The incidence of any improvement of reticulin to a grade of ≤ 2 for subjects who developed grade 3 reticulin after initial exposure to romiplostim as measured by the modified Bauermeister grading scale [ Time Frame: At Year 1, Year 2, or Year 3 post romiplostim exposure ] [ Designated as safety issue: Yes ]
  • The incidence of CTCAE grade ≥ 2 shift in anemia or neutropenia post romiplostim exposure [ Time Frame: from Screening through End of Study (maximum total time estimated to be approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
  • The incidence and severity of all adverse events including clinically significant changes in laboratory values [ Time Frame: from Screening through End of Study (maximum total time estimated to be approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
  • To investigate any changes between each sampling of four cytokines (TGF- β1, PDGF, OPG and bFGF), and any correlation of these changes with bone marrow biopsies, clinical and laboratory findings [ Time Frame: At Week 12 and at Year 1, Year 2, or Year 3 of romiplostim exposure ] [ Designated as safety issue: Yes ]
  • The incidence of neutralizing antibody formation to romiplostim or cross-reacting antibodies to endogenous thrombopoietin [ Time Frame: from Screening through End of Study (maximum total time estimated to be approximately 3 years + 3 months) ] [ Designated as safety issue: Yes ]
  • The incidence of collagen fibrosis as evidenced by trichrome staining in subjects who developed collagen fibrosis at Yrs 1, 2, or 3 after initial exposure of romiplostim using modified Bauermeister grading scale [ Time Frame: 12 wks after romiplostim discontinuation ] [ Designated as safety issue: Yes ]
  • The incidence of bone marrow reticulin increases by ≥ 2 severity grades or increase to grade 4 over baseline as evidenced by reticulin silver staining using the modified Bauermeister grading scale [ Time Frame: At Year 1, Year 2, or Year 3 post romiplostim exposure ] [ Designated as safety issue: Yes ]

Enrollment: 169
Study Start Date: August 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Year 2
Bone Marrow Biopsy at baseline and Year 2
Biological: romiplostim
Romiplostim will be administered weekly by SC injection for 3 years at a starting dose of 1 mcg/kg.
Experimental: Year 3
Bone Marrow Biopsy at baseline and Year 3
Biological: romiplostim
Romiplostim will be administered weekly by SC injection for 3 years at a starting dose of 1 mcg/kg.
Experimental: Year 1
Bone Marrow Biopsy at baseline and Year 1
Biological: romiplostim
Romiplostim will be administered weekly by SC injection for 3 years at a starting dose of 1 mcg/kg.

Detailed Description:

This is a prospective, phase IV, multi-center, open label, study evaluating the changes in bone marrow reticulin and collagen in adult subjects receiving romiplostim for the treatment of thrombocytopenia associated with ITP.

The purpose of this study is to evaluate changes in bone marrow morphology (structure) after long-term exposure to romiplostim.

Subjects, diagnosed with ITP according to the ASH Guidelines, will be sequentially enrolled into the following groups:

  • Bone marrow biopsy at baseline and Year 1
  • Bone marrow biopsy at baseline and Year 2
  • Bone marrow biopsy at baseline and Year 3

All subjects will receive romiplostim for 3 years, unless withdrawn from the study early. All subjects will return for 1 visit post treatment for End of Study (EOS) procedures.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of ITP according to American Society of Hematology (ASH) guidelines
  • Subject must have had a bone marrow biopsy within one year prior to planned first dose of romiplostim (with available bone marrow tissue block or unstained histological slides to send to a central laboratory for interpretation) or must consent to a pre-treatment bone marrow biopsy within 3 weeks prior to planned first dose of romiplostim. Central laboratory interpretation is required prior to first dose of romiplostim
  • Subject must agree to a scheduled bone marrow biopsy at Year 1, Year 2, or Year 3 following romiplostim treatment and any unscheduled biopsies if clinically indicated
  • Subject ≥18 years of age
  • Baseline bone marrow reticulin grade of 0, 1, 2, or 3 according to the modified Bauermeister grading scheme as assessed by central laboratory interpretation
  • Platelet count < 50 x 10^9/L
  • Must have received at least 1 prior ITP therapy (examples of ITP therapy include corticosteroids, IVIG, splenectomy)
  • Subject (or legally-acceptable representative) is willing and able to provide written informed consent

Exclusion Criteria:

  • Baseline bone marrow biopsy positive for collagen fibrosis
  • Any known history of or currently active bone marrow stem cell disorder, hematological malignancy, myeloproliferative disorder, myelodysplastic syndrome
  • Any current active malignancy
  • Any prior exposure to cytostatic chemotherapy or radiotherapy for malignancy
  • Subject has undergone pacemaker placement, cardiac ablation of arrhythmia, and/or any current treatment with Vaughan Williams Class IA - IC and Class III agents (Vaughan Williams, 1970)
  • Subject has participated in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), or thrombopoietin receptor agonists (ie romiplostim or eltrombopag)
  • Subject has a known hypersensitivity to any recombinant E coli-derived product
  • Subject is currently enrolled in or has not yet completed (at least 4 weeks since ending) other investigational device or drug trial(s) or subject is receiving other investigational agent(s)
  • Other investigational procedures are excluded
  • Subject of child-bearing potential is evidently pregnant (eg positive pregnancy test) or is breast feeding
  • Subject is not using adequate contraceptive precautions
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative and/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: NCT00907478

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

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00907478     History of Changes
Other Study ID Numbers: 20080009
Study First Received: May 21, 2009
Last Updated: June 23, 2014
Health Authority: Australia: Therapeutic Goods Administration
Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Austria: Bundesamt fur Sicherheit im Gesundheitswesen
Austria: Bundesamt für Sicherheit im Gesundheitswesen
Belgium: Ministry of Health
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Canada: Health Products and Food Branch
Czech Republic: State Institute for Drug Control
Estonia: State Agency of Medicines
European Union: European Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Lithuania: State Medicines Control Agency of Lithuania
Mexico: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romaina: National Medicines Agency
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: State Institiute for Drug Control
Slovenia: Agency for Medicinal Products and Medicinal Devices of the Republic of Slovenia (ARSZMP)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Lakemedelsverket
United States: Food and Drug Administration
United States: Chesapeake Institutional Review Board (CIRB)

Keywords provided by Amgen:
Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenia Purpura
Immune Thrombocytopenic Purpura
Immune Thrombocytopenia
ITP

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Thrombocytopenia
Autoimmune Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Hemorrhage
Hemorrhagic Disorders
Immune System Diseases
Pathologic Processes
Signs and Symptoms
Skin Manifestations
Thrombotic Microangiopathies

ClinicalTrials.gov processed this record on October 30, 2014