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Eltrombopag and the Bcl-extra-large (xL) Pathway in Idiopathic Thrombocytopenic Purpura (ITP)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
James B. Bussel, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00902018
First received: May 8, 2009
Last updated: January 31, 2017
Last verified: January 2017

May 8, 2009
January 31, 2017
January 2009
September 7, 2015   (Final data collection date for primary outcome measure)
To determine how eltrombopag affects platelet counts. [ Time Frame: 2-4 weeks. ]
Same as current
Complete list of historical versions of study NCT00902018 on ClinicalTrials.gov Archive Site
  • To determine effect of eltrombopag on platelet apoptosis. [ Time Frame: First two weeks of study. ]
  • To determine how eltrombopag affects platelet function and platelet survival. [ Time Frame: First two weeks of study. ]
  • To continue to assess the safety and efficacy of eltrombopag. [ Time Frame: First two weeks of study. ]
Same as current
Not Provided
Not Provided
 
Eltrombopag and the Bcl-extra-large (xL) Pathway in Idiopathic Thrombocytopenic Purpura (ITP)
The Effect of Eltrombopag on Platelet Survival: the Role of the B-cell Lymphoma Extra Large (BcL-xL) Pathway
The purpose of this study is to further evaluate the effects that eltrombopag has on platelets in subjects with chronic ITP. Eltrombopag is approved by the Food and Drug Administration (FDA) for the treatment of low platelets in patients with chronic ITP. It is being further studied by GlaxoSmithKline in other conditions associated with low platelets. This research study is being done because eltrombopag has been shown to increase platelet counts in a different way than other therapies for ITP. The investigators want to further study how eltrombopag affects subjects and their platelets to determine how the study drug should best be used in ITP treatment.
The B-cell lymphoma extra large (Bcl-xL/Bak) balance has been identified as an intrinsic mechanism that is critical in determining platelet lifespan (Mason, Cell 2007). There is evidence that Bcl-xL protein expression in megakaryocytes is regulated by Thrombopoietin (TPO) mediated activation of Akt pathways mediated by Jak2 and Stat 5 (possibly by Stat 3 as well). (e.g., Kozuma et. al., Journal of Thrombosis and Haemostasis). Little is known about the Bcl-xL / Bak axis in patients with ITP, or the effect of TPO-R stimulation on platelet survival in patients with ITP. The TPO effect may be a result of stimulation of thrombopoietin-receptor (TPO-R) signalling in megakaryocytes altering the packaging of Bcl-xl into platelets, or be a direct effect of platelet TPO-R stimulation as described above.
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Idiopathic Thrombocytopenic Purpura
Drug: Promacta (eltrombopag)
Subjects will be treated with eltrombopag 75 mg once daily. Patients will be monitored 3 times a week for the first 2 weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for 3-4 months.
no arm
No Arm
Intervention: Drug: Promacta (eltrombopag)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
September 7, 2015
September 7, 2015   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subject has signed and dated a written informed consent
  • Male or female adults (≥18 years) diagnosed with either primary ITP according to the American Society for Hematology or British Committee for Standards in Haematology (ASH/BCSH) guidelines [Blood, 1996; British Journal of Haematology, 2003] for at least three months prior to study entry or with ITP secondary to Evans syndrome, systemic lupus erythematosus (SLE), or Common Variable Immunodeficiency (including hypogammaglobulinemia).
  • Subjects must have responded with a platelet count > 30,000/µL to a previous ITP therapy including thrombopoietic agents.
  • Platelet count < 30,000/µL
  • Female subjects of childbearing potential are practicing an acceptable method of contraception or are completely abstinent from intercourse.

Exclusion Criteria:

  • Active infection
  • Previously treated with thrombopoietic agents IF either no response at a therapeutic dose (peak platelet count < 50k) OR treatment with the agent within the past 4 weeks
  • Currently treated with concomitant ITP medication that has not been stable in dose for at least 2 weeks - only prednisone, azathioprin, and danazol are allowed.
  • Female subjects who are nursing or pregnant
  • Thrombosis of any kind within past 6 months or on blood thinners because of thrombosis.
  • Intravenous Immunoglobulin (IVIG), IV anti-D, bolus corticosteroids or vinca alkaloids within the past week
  • Other cytotoxic or immunosuppressive ITP therapy within the past 8 weeks or rituximab within the past 12 weeks
  • Active non-dermatologic malignancy defined as presence of known tumor ie. visible by radiography or evident on blood or bone marrow testing OR receiving chemotherapy within past 2 months
  • Hemoglobin < 10 gm/dl or white blood cell count < 2,500/ul
  • Liver function tests (ALT, Aspartate Aminotransferase (AST), or total bilirubin) > three times upper limit of normal (ULN)
  • Creatinine > two times upper limit of normal (ULN)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00902018
0809009980
No
Not Provided
Not Provided
Not Provided
James B. Bussel, Weill Medical College of Cornell University
Weill Medical College of Cornell University
GlaxoSmithKline
Principal Investigator: James B. Bussel, MD Weill Medical College of Cornell University
Weill Medical College of Cornell University
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP