Clinical trial NCT01098487: A Longitudinal 2-year Bone Marrow Study of Eltrombopag in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Official title: A Longitudinal 2-year Bone Marrow Study of Eltrombopag Olamine (SB-497115-GR) in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Purpura, Thrombocytopaenic, Idiopathic
Keywords: Immune (idiopathic) thrombocytopenic purpura (ITP)
bone marrow fibers
eltrombopag olamine
thrombopoietin receptor agonist
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-04-02
Enrollment: 167
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: A open-label, multi-center 2-year safety study to ascertain the baseline levels of bone marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP) and to evaluate the long-term effect of eltrombopag on bone marrow fibers. The study will also describe the long-term safety and tolerability of oral eltrombopag treatment in subjects with chronic ITP.

Detailed description: This is a phase IV, open-label safety study, designed to determine baseline levels of bone marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP)and to evaluate the long-term effect of eltrombopag on bone marrow reticulin and/or collagen fibers.

The duration of the screening period is up to 8 weeks. Eltrombopag will be administered for at least 2-years followed by a 4-week follow-up period. Bone marrow biopsies will be performed at screening, after 1-year and 2-years of eltrombopag treatment, and at early withdrawal of treatment. The screening bone marrow biopsy should be performed within 8 weeks of planned start of study medication and the bone marrow biopsy block must be available for central laboratory processing.

Eligibility criteria: Inclusion Criteria:

* Subjects must have signed and dated a written informed consent and be able to understand and comply with protocol requirements and instructions.
* Adults (≥18 years) diagnosed with chronic ITP according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines \[George, 1996; BCSH, 2003; Provan, 2009\]. In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other disease causative of thrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physical examination should not suggest any disease, which may cause thrombocytopenia other than ITP.
* Subjects must be physically eligible for serial bone marrow biopsies and must have a bone marrow biopsy performed during screening, and be willing to remain on the study for at least 2 years with annual bone marrow biopsies.
* Subjects, who previously received eltrombopag or romiplostim, must have completed treatment with these therapies at least 6 months prior to the screening bone marrow biopsy.
* Subjects must have the following clinical chemistry values:
* ALT and AST \< 2xULN;
* Bilirubin \<1.5xULN (except for Gilbert's Syndrome);
* Subjects are practicing an acceptable method of contraception as specified in the protocol.
* In France, subjects will be eligible for inclusion in this study, only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Subjects with any clinically relevant abnormality, other than ITP, or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
* Subjects with any concurrent malignant disease and/or a recent history of cancer treatment with systemic chemotherapy and/or radiotherapy.

Exception: Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

* Subjects with any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), AND ≥ two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, etc), or any family history of arterial or venous thrombosis.
* Subjects with screening bone marrow fibers of either MF Grade 3 using European Consensus scale or Grade 4 using Bauermeister scale.
* Subjects with a QTc \>450 msec or \> 480 msec for subjects with Bundle Branch Block.
* Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotrophin (β-hCG) pregnancy test) at screening.
* Subjects treated with an investigational drug (other than a thrombopopoetin-receptor (TPO-R) agonist) within 30 days or five half-lives (whichever is longer) preceding the first dose of eltrombopag in the study. (For romiplostim or eltrombopag, see inclusion criterion #4).
* Subjects treated with any TPO-R agonist other than romiplostim or eltrombopag.
* Subjects with recent history of alcohol/drug abuse as determined by the investigator.

Primary outcomes:
measure: Number of Participants With Bone Marrow (BM) Fibers of MF Grade 0, 1, 2 and 3 on the European Consensus (EC) Scale at Baseline
timeFrame: Baseline
measure: Number of Participants With a Positive or Negative Collagen Level at Baseline
timeFrame: Baseline
measure: Number of Participants With Indicated Grade Change From Baseline in the EC Grading Scale at 1 Year
timeFrame: Baseline and 1 year
measure: Number of Participants With Indicated Change From Baseline in the EC Grading Scale at 2 Years
timeFrame: Baseline and 2 years
measure: Number of Participants With a Positive or Negative Collagen Level at 1 Year
timeFrame: 1 year
measure: Number of Participants With a Positive or Negative Collagen Level at 2 Year
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters at Any Time Post-Baseline During the Study
timeFrame: From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years)
measure: Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Hematology Parameters at Any Time Post-Baseline During the Study
timeFrame: From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years)
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Started On-therapy + 1 Day, >1 to 30 Days Post Therapy and >30 Days Post Therapy
timeFrame: From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years)
Other outcomes:
Locations:
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Hradec Kralove
country: Czech Republic
facility: GSK Investigational Site
city: Olomouc
country: Czech Republic
facility: GSK Investigational Site
city: Praha 2
country: Czech Republic
facility: GSK Investigational Site
city: Caen cedex 9
country: France
facility: GSK Investigational Site
city: Créteil
country: France
facility: GSK Investigational Site
city: Pessac Cedex
country: France
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Shatin, New Territories
country: Hong Kong
facility: GSK Investigational Site
city: Debrecen
country: Hungary
facility: GSK Investigational Site
city: Győr
country: Hungary
facility: GSK Investigational Site
city: Szeged
country: Hungary
facility: GSK Investigational Site
city: Ludhiana
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Surat
country: India
facility: GSK Investigational Site
city: Vellore
country: India
facility: GSK Investigational Site
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Vicenza
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Seongnam-si Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Karachi
country: Pakistan
facility: GSK Investigational Site
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wong RS, Bakshi K, Brainsky A. Thrombophilia in patients with chronic immune thrombocytopenia. Scand J Clin Lab Invest. 2015 Jan;75(1):13-7. doi: 10.3109/00365513.2014.962597. Epub 2014 Oct 9.