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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00902018
Recruitment Status : Completed
First Posted : May 14, 2009
Last Update Posted : February 2, 2017
Information provided by (Responsible Party):
James B. Bussel, Weill Medical College of Cornell University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Idiopathic Thrombocytopenic Purpura Drug: Promacta (eltrombopag) Phase 2

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Eltrombopag on Platelet Survival: the Role of the B-cell Lymphoma Extra Large (BcL-xL) Pathway
Study Start Date : January 2009
Actual Primary Completion Date : September 7, 2015
Actual Study Completion Date : September 7, 2015

Arm Intervention/treatment
no arm
No Arm
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.

Primary Outcome Measures :
  1. To determine how eltrombopag affects platelet counts. [ Time Frame: 2-4 weeks. ]

Secondary Outcome Measures :
  1. To determine effect of eltrombopag on platelet apoptosis. [ Time Frame: First two weeks of study. ]
  2. To determine how eltrombopag affects platelet function and platelet survival. [ Time Frame: First two weeks of study. ]
  3. To continue to assess the safety and efficacy of eltrombopag. [ Time Frame: First two weeks of study. ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00902018

United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
Sponsors and Collaborators
Weill Medical College of Cornell University
Principal Investigator: James B. Bussel, MD Weill Medical College of Cornell University

Responsible Party: James B. Bussel, The Effect of Eltrombopag on Platelet Survival: the Role of the BcL-xL Pathway, Weill Medical College of Cornell University Identifier: NCT00902018     History of Changes
Other Study ID Numbers: 0809009980
First Posted: May 14, 2009    Key Record Dates
Last Update Posted: February 2, 2017
Last Verified: January 2017

Keywords provided by James B. Bussel, Weill Medical College of Cornell University:

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases