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

Amgen

Status and phase: Completed; Phase 4

Conditions: Thrombocytopenia; Idiopathic Thrombocytopenic Purpura

Treatments: Biological: romiplostim

Study type: Interventional

Funder types: Industry

Identifiers

NCT00907478

20080009

Details and patient eligibility

About

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

Full 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All participants received romiplostim for 3 years, unless withdrawn from the study early.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one visit for End of Study (EOS) procedures 4 weeks after romiplostim discontinuation, or, for participants who were withdrawn from the study due to the presence of collagen fibrosis, or had a change to grade 3 reticulin, at 12 weeks after discontinuation of romiplostim.

Enrollment: 169 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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169 participants in 1 patient group

Romiplostim

Experimental group

Description:

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.

Treatment:

Biological: romiplostim