Eltrombopag and the Bcl-xL Pathway in Idiopathic Thrombocytopenic Purpura (ITP) - Full Text View

Sponsor:	Weill Medical College of Cornell University
Collaborator:	GlaxoSmithKline
Information provided by:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00902018

Purpose

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	Intervention	Phase
Idiopathic Thrombocytopenic Purpura	Drug: Promacta (eltrombopag)	Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Effect of Eltrombopag on Platelet Survival: the Role of the BcL-xL Pathway

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia MYH9-related disorder thrombotic thrombocytopenic purpura

Drug Information available for: Eltrombopag

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:

To determine how eltrombopag affects platelet counts. [ Time Frame: 2-4 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine effect of eltrombopag on platelet apoptosis. [ Time Frame: First two weeks of study. ] [ Designated as safety issue: Yes ]
To determine how eltrombopag affects platelet function and platelet survival. [ Time Frame: First two weeks of study. ] [ Designated as safety issue: Yes ]
To continue to assess the safety and efficacy of eltrombopag. [ Time Frame: First two weeks of study. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	12
Study Start Date:	May 2009
Estimated Study Completion Date:	January 2012
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Detailed Description:

The 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 TPO-mediated activation of Akt pathways mediated by Jak2 and Stat 5 (possibly by Stat 3 as well). (e.g. Kozuma et al, J Thromb Haemost 2007). 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 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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, 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.
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 WBC < 2,500/ul
Liver function tests (ALT, AST, or T Bili) > 3X ULN
Creatinine > 2X ULN

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00902018

Contacts

Contact: James B Bussel, MD

212-746-3474

jbussel@med.cornell.edu

Locations

United States, New York
Weill Cornell Medical College	Recruiting
New York, New York, United States, 10065
Contact: James B Bussel, MD 212-746-3474 jbussel@med.cornell.edu

Sponsors and Collaborators

Weill Medical College of Cornell University

GlaxoSmithKline

Investigators

Principal Investigator:

James B Bussel, MD

Weill Medical College of Cornell University

More Information

No publications provided

Responsible Party:	James Bussel, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier:	NCT00902018 History of Changes
Other Study ID Numbers:	0809009980
Study First Received:	May 8, 2009
Last Updated:	June 13, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:

ITP

Additional relevant MeSH terms:

Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations

Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on May 24, 2012