A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients
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|ClinicalTrials.gov Identifier: NCT00922883|
Recruitment Status : Completed
First Posted : June 17, 2009
Results First Posted : July 16, 2018
Last Update Posted : October 20, 2020
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Completion Date :||April 24, 2018|
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.
Other Name: Promacta
- 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).
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
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Cynthia E Dunbar, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|