Clinical trial NCT00907478: Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
Keywords: Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenia Purpura
Immune Thrombocytopenic Purpura
Immune Thrombocytopenia
ITP
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-05-22
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: Participants diagnosed with ITP according to the American Society of Hematology (ASH) Guidelines were 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All participants received romiplostim for 3 years, unless withdrawn from the study early. Participants returned for one visit for End of Study (EOS) procedures 4 weeks after romiplostim discontinuation, or, for participants who were withdrawn from the study due to the presence of collagen fibrosis, or had a change to grade 3 reticulin, at 12 weeks after discontinuation of romiplostim.

Eligibility 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, intravenous immunoglobulin \[IVIG\], 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 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.

Primary outcomes:
measure: Percentage of Participants With Collagen Fibrosis
timeFrame: At Years 1, 2 or 3 after initial exposure of romiplostim
Secondary outcomes:
measure: Number of Participants With Collagen Fibrosis 12 Weeks After Romiplostim Discontinuation in Participants Who Developed Collagen Fibrosis at Years 1, 2, or 3
timeFrame: 12 weeks after romiplostim discontinuation
measure: Percentage of Participants Who Developed an Increased Modified Bauermeister Grade
timeFrame: At Year 1, Year 2, or Year 3 post romiplostim exposure
measure: Percentage of Participants With Clinically Relevant Changes in Total Cardiac Output Corrected (QTc) Intervals
timeFrame: Baseline, Week 3 and Week 12
measure: Number of Participants With Improvement of Reticulin to a Grade of ≤ 2 for Participants Who Developed Grade 3 Reticulin
timeFrame: 12 weeks after romiplostim discontinuation
measure: Percentage of Participants With CTCAE Grade ≥ 2 Shift in Anemia or Neutropenia
timeFrame: 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.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
measure: Number of Participants Who Developed Antibodies or Neutralizing Antibodies to Romiplostim or to Endogenous Thrombopoietin
timeFrame: Every 24 weeks and at the end of study visit (4 weeks or 12 weeks after study drug discontinuation).
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.