A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Aplastic Anemia Patients With Immunosuppressive-Therapy Refractory Thrombocytopenia

A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Aplastic Anemia Patients With Immunosuppressive-Therapy Refractory Thrombocytopenia
This study is currently recruiting participants.
Verified February 2012 by National Institutes of Health Clinical Center (CC)

First Received on June 16, 2009.  
Last Updated on June 28, 2012  
History of Changes
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00922883

Severe aplastic anemia (SAA) is a life-threatening blood disease which can be effectively treated with immunosuppressive drug regimens or allogeneic stem cell transplantation. However, 20-40% of patients without transplant options do not respond to immunosuppressive therapies, and have persistent severe thrombocytopenia. Even patients that respond to immunosuppressive therapies with an improvement in their life-threatening neutropenia sometimes have persistent thrombocytopenia. Both groups of patients (i.e. nonresponders to immunosuppressive therapy and responders with persistent thrombocytopenia) require regular platelet transfusions, which are expensive and inconvenient, and are a risk for further serious bleeding complications.

Thrombopoietin (TPO) is the principal endogenous regulator of platelet production. On binding to the megakaryocyte progenitor TPO receptor, TPO initiates a number of signal transduction events to increase the production of mature megakaryocytes and platelets. Thrombopoietin also has stimulatory effects on more primitive multilineage progenitors and stem cells in vitro and in animal models. A 2nd generation small molecule TPO-agonist, eltrombopag (Promacta(Registered Trademark)) has been shown to increase platelets in healthy subjects and in thrombocytopenic patients with chronic immune thrombocytopenic purpura (ITP) and hepatitis C virus (HCV) infection. Eltrombopag is administered orally and has been well-tolerated in clinical trials. Unlike recombinant TPO, it has not been found to induce autoantibodies. Eltrombopag received FDA accelerated approval on Nov 20, 2008 for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Because a paucity of megakaryocytes and decreased platelet production is responsible for thrombocytopenia in aplastic anemia patients, we now propose this Phase 2, non-randomized pilot study of eltrombopag in aplastic anemia patients with immunosuppressive therapy refractory thrombocytopenia.

Subjects will initiate study medication at an oral dose of 50 mg/day (25 mg/day for East Asians), which will be increased or decreased as clinically indicated to the lowest dose that maintains a stable platelet count 20,000/(micro)L above baseline while maximizing tolerability. Treatment response is defined as platelet count increases to 20,000/(micro)L above baseline at three months. Subjects with response at 3 months may continue study medication (extended access) until they meet an off study criteria.

Condition Intervention Phase
Anemia, Aplastic
Anemia, Hypoplastic
Drug: Eltrombopag (Promacta)
Drug: Eltrombopag
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Aplastic Anemia Patients With Immunosuppressive-Therapy Refractory Thrombocytopenia

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

  • The portion of drug responders as defined by changes in the platelet count and/or platelet transfusion requirements and the toxicity profile as measured at 12 weeks using the CTCAE criteria. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

  • Incidence of bleeding; changes in serum thrombopoietin level (as measured by enzyme-linked immunosorbent assay, R& D Systems), and health related quality of life (as measured by the Medical Outcomes Study 36-item Short Form General Health Su…

Estimated Enrollment: 45
Study Start Date: May 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Intervention Details:

    Drug: Eltrombopag (Promacta)


    Drug: Eltrombopag


Show Detailed Description


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

    1. Diagnosis of aplastic anemia, with refractory thrombocytopenia following at least one treatment course of horse or rabbit ATG/cyclosporine.
    2. Platelet count less than or equal to 30,000/microL
    3. Age greater than or equal to 18 years old


  1. Diagnosis of Fanconi anemia
  2. Infection not adequately responding to appropriate therapy
  3. Patients with a PNH clone size in neutrophils of greater than or equal to 50%
  4. HIV positivity
  5. Creatinine > 2.5
  6. Bilirubin > 2.0
  7. SGOT or SGPT > 5 times the upper limit of normal
  8. Hypersensitivity to eltrombopag or its components
  9. Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
  10. History of malignancy other than localized tumors diagnosed more than one year previously and treated surgically with curative intent (for instance squamous cell or other skin cancers, stage 1 breast cancer, cervical carcinoma in situ, etc)
  11. Unable to understand the investigational nature of the study or give informed consent
  12. History of congestive heart failure arrhythmia requiring chronic treatment, arterial or venous thrombosis (not excluding line thrombosis) within the last 1 year, or myocardial infarction within 3 months before enrollment
  13. ECOG Performance Status of 3 or greater
  14. Treatment with horse or rabbit ATG or Campath within 6 months of study entry. Concurrent stable treatment with cyclosporine or G-CSF is permitted.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00922883

Contact: Susan Soto, R.N. (301) 402-0797 jordansk@cc.nih.gov
Contact: Ronan G Desmond, M.D. (301) 451-7143 desmondrg@mail.nih.gov

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: Susan Soto     301-402-0797     jordansk@cc.nih.gov    
Sponsors and Collaborators
Principal Investigator: Ronan G Desmond, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:


Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Matthew J. Olnes, M.D./National Heart, Lung, and Blood Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00922883    
History of Changes
Other Study ID Numbers: 090154, 09-H-0154
Study First Received: June 16, 2009
Last Updated: June 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Aplastic Anemia

Additional relevant MeSH terms:

Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Blood Platelet Disorders
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2012

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