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A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients

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ClinicalTrials.gov Identifier: NCT00922883
Recruitment Status : Active, not recruiting
First Posted : June 17, 2009
Results First Posted : July 16, 2018
Last Update Posted : August 15, 2018
Sponsor:
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 cytopenias, requiring 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 and also stimulates hematopoietic stem and progenitor cells. A small molecule oral TPO-agonist, eltrombopag has been shown to increase platelets in healthy subjects and in patients with immune thrombocytopenic purpura (ITP), and received FDA approval in 2008 for the treatment of thrombocytopenia in ITP. This Phase 2, non-randomized pilot study of eltrombopag in aplastic anemia patients with immunosuppressive therapy refractory thrombocytopenia will test the safety and potential efficacy of eltrombopag treatment patients with refractory thrombocytopenia following immunosuppression for aplastic anemia.

Subjects will initiate study medication at an oral dose of 50 mg/day, which will be increased up to 150 mg/day as clinically indicated to the lowest dose that maintains a stable platelet count 20,000/(micro)L above baseline while maximizing tolerability. Response will be assessed at 3-4 months. Platelet response is defined as platelet count increases to 20,000/L above baseline at three months. or stable platelet counts with transfusion independence for a minimum of 8 weeks. Erythroid response for subjects with a pretreatment hemoglobin of less than 9 g/dL will be defined as an increase in hemoglobin by greater than or equal to 1.5g/dL without packed red blood cell (PRBC) transfusion support, or a reduction in the units of transfusions by an absolute number of at least 4 PRBC transfusions for eight consecutive weeks compared with the pretreatment transfusion number in the previous 8 weeks. Neutrophil response will be defined in those with a pretreatment absolute neutrophil count (ANC) of less than 0.5 times 10(9)/L as at least a 100 percent increase or an absolute increase greater than 0.5 times 10(9)/L. Subjects with response at 3-4 months may continue study medication (extended access) until they meet an off study criteria. The primary objective is to assess the safety and efficacy of the oral thrombopoietin receptor agonist (TPO-R agonist) eltrombopag in aplastic anemia patients with immunosuppressive-therapy refractory thrombocytopenia. Secondary objectives include the analysis of the incidence and severity of bleeding episodes, and the impact on quality of life.


Condition or disease Intervention/treatment Phase
Anemia, Aplastic Anemia, Hypoplastic Thrombocytopenia Drug: Eltrombopag Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 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
Eltrombopag (Promacta): Subjects commenced eltrombopag at a dose of 50 mg, which was increased by 25 mg every 2 weeks if the platelet count had not increased by 20 × 103/µL, to a maximum dose of 150 mg.
Drug: Eltrombopag
Other Name: Promacta




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
Criteria
  • INCLUSION CRITERIA:

    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

EXCLUSION CRITERIA:

  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 ClinicalTrials.gov identifier (NCT number): NCT00922883


Locations
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)
Investigators
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)
ClinicalTrials.gov Identifier: NCT00922883     History of Changes
Other Study ID Numbers: 090154
09-H-0154 ( Other Identifier: The National Institutes of Health )
First Posted: June 17, 2009    Key Record Dates
Results First Posted: July 16, 2018
Last Update Posted: August 15, 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) ):
Promacta
SAA
Aplastic Anemia
Thrombocytopenia

Additional relevant MeSH terms:
Anemia
Thrombocytopenia
Anemia, Aplastic
Hematologic Diseases
Blood Platelet Disorders
Bone Marrow Diseases