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

NCT00907478 | Completed Phase 4 Results

• 1 other identifier: 20080009
• Study Type: interventional
• Target: 169
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Thrombocytopenia; Idiopathic Thrombocytopenic Purpura

Keywords

Idiopathic Thrombocytopenic Purpura; Idiopathic Thrombocytopenia Purpura; Immune Thrombocytopenic Purpura; Immune Thrombocytopenia; ITP

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Collagen Fibrosis

  The percentage of participants who developed collagen fibrosis as evidenced by trichrome staining. Bone marrow biopsy samples were assessed using the modified Bauermeister grading scale by a central laboratory.

  At Years 1, 2 or 3 after initial exposure of romiplostim

Secondary Outcomes (7)

• Number of Participants With Collagen Fibrosis 12 Weeks After Romiplostim Discontinuation in Participants Who Developed Collagen Fibrosis at Years 1, 2, or 3

  12 weeks after romiplostim discontinuation

• Percentage of Participants Who Developed an Increased Modified Bauermeister Grade

  At Year 1, Year 2, or Year 3 post romiplostim exposure

• Percentage of Participants With Clinically Relevant Changes in Total Cardiac Output Corrected (QTc) Intervals

  Baseline, Week 3 and Week 12

• Number of Participants With Improvement of Reticulin to a Grade of ≤ 2 for Participants Who Developed Grade 3 Reticulin

  12 weeks after romiplostim discontinuation

• Percentage of Participants With CTCAE Grade ≥ 2 Shift in Anemia or Neutropenia

  From the first dose of study drug until 4 weeks after treatment discontinuation or 12 weeks after treatment discontinuation for patients who developed collagen fibrosis or a change to grade 3 reticulin; the overall median treatment duration was 154 weeks.

Study Arms (1)

Romiplostim

EXPERIMENTAL

Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose of romiplostim was 1 μg/kg; weekly dose increases continued in increments of 1 μg/kg/week to a maximum dose of 10 μg/kg in an attempt to reach a target platelet count of ≥ 50 x 10\^9/L.

Biological: romiplostim

Interventions

romiplostim BIOLOGICAL

Romiplostim administered by subcutaneous injection

Also known as: Nplate®

Romiplostim

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, intravenous immunoglobulin \[IVIG\], splenectomy)
• Subject (or legally-acceptable representative) is willing and able to provide written informed consent

You may not qualify if:

• 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 pegylated recombinant human megakaryocyte growth and development factor (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.

Sponsors & Collaborators

• Amgen: lead

Related Publications (4)

• Janssens A, Rodeghiero F, Anderson D, Chong BH, Boda Z, Pabinger I, Cervinek L, Terrell DR, Wang X, Franklin J. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Ann Hematol. 2016 Jun;95(7):1077-87. doi: 10.1007/s00277-016-2682-2. Epub 2016 Apr 30.

  PMID: 27130310 BACKGROUND

• Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, Lyons R, Garcia-Chavez J, Carpenter N, Wang X, Eisen M. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017 Aug;102(8):1342-1351. doi: 10.3324/haematol.2016.161968. Epub 2017 Apr 14.

  PMID: 28411254 BACKGROUND

• Kuter DJ, Newland A, Chong BH, Rodeghiero F, Romero MT, Pabinger I, Chen Y, Wang K, Mehta B, Eisen M. Romiplostim in adult patients with newly diagnosed or persistent immune thrombocytopenia (ITP) for up to 1 year and in those with chronic ITP for more than 1 year: a subgroup analysis of integrated data from completed romiplostim studies. Br J Haematol. 2019 May;185(3):503-513. doi: 10.1111/bjh.15803. Epub 2019 Feb 21.

  PMID: 30793285 BACKGROUND

• Kuter DJ, Arnold DM, Rodeghiero F, Janssens A, Selleslag D, Bird R, Newland A, Mayer J, Wang K, Olie R. Safety and efficacy of self-administered romiplostim in patients with immune thrombocytopenia: Results of an integrated database of five clinical trials. Am J Hematol. 2020 Jun;95(6):643-651. doi: 10.1002/ajh.25776. Epub 2020 Mar 21.

  PMID: 32129511 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic

Interventions

romiplostim

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 22, 2009
• Study Start: August 11, 2009
• Primary Completion: January 9, 2014
• Study Completion: January 14, 2014
• Last Updated: September 21, 2022
• Results First Posted: January 1, 2015

Record last verified: 2022-09