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

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: NCT00922883
Recruitment Status : Active, not recruiting
First Posted : June 17, 2009
Results First Posted : July 16, 2018
Last Update Posted : July 16, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:

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 ) 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 or disease Intervention/treatment Phase
Anemia, Aplastic Anemia, Hypoplastic Thrombocytopenia Drug: Eltrombopag (Promacta) Drug: Eltrombopag Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 29, 2009
Actual Primary Completion Date : May 7, 2013
Estimated Study Completion Date : August 31, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Eltrombopag

Arm Intervention/treatment
Experimental: Eltrombopag Drug: Eltrombopag (Promacta)
Drug: Eltrombopag

Primary Outcome Measures :
  1. The Portion of Drug Responders as Defined by Hematologic Improvements [ Time Frame: 12-16 weeks ]
    Defined as unilineage or multilineage recovery by 1 or more of the following: 1) platelet response (increase to 20 × 103/μL above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks in those who were transfusion dependent on entry into the protocol); (2) erythroid response (when pretreatment hemoglobin was <9 g/dL, defined as an increase in hemoglobin by 1.5 g/dL or, in transfused patients, a reduction in the units of packed red blood cell transfusions by an absolute number of at least 4 transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks); and (3) neutrophil response (when pretreatment absolute neutrophil count [ANC] of <0.5 × 103/μL as at least a 100% increase in ANC, or an ANC increase >0.5 × 103/μL, and the toxicity profile as measured using Common Terminology Criteria for Adverse Events).

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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 12 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.

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): NCT00922883

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Cynthia E Dunbar, M.D. National Heart, Lung, and Blood Institute (NHLBI)

Additional Information:
Publications of Results:
Other Publications:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI) Identifier: NCT00922883     History of Changes
Other Study ID Numbers: 090154
First Posted: June 17, 2009    Key Record Dates
Results First Posted: July 16, 2018
Last Update Posted: July 16, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Aplastic Anemia

Additional relevant MeSH terms:
Anemia, Aplastic
Hematologic Diseases
Blood Platelet Disorders
Bone Marrow Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs