A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients
Status:
Completed
Trial end date:
2018-04-24
Target enrollment:
Participant gender:
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.