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

Information source: Weill Medical College of Cornell University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Idiopathic Thrombocytopenic Purpura

Intervention: Promacta (eltrombopag) (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Weill Medical College of Cornell University

Official(s) and/or principal investigator(s):
James B Bussel, MD, Principal Investigator, Affiliation: Weill Medical College of Cornell University

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.

Clinical Details

Official title: The Effect of Eltrombopag on Platelet Survival: the Role of the BcL-xL Pathway

Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To determine how eltrombopag affects platelet counts.

Secondary outcome:

To determine effect of eltrombopag on platelet apoptosis.

To determine how eltrombopag affects platelet function and platelet survival.

To continue to assess the safety and efficacy of eltrombopag.

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Weill Cornell Medical College, New York, New York 10065, United States
Additional Information

Starting date: May 2009
Last updated: November 14, 2012

Page last updated: August 23, 2015

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