A Randomized Placebo-controlled Phase 2 Study of Decitabine With or Without Eltrombopag in AML Patients
Status:
Unknown status
Trial end date:
2019-05-01
Target enrollment:
Participant gender:
Summary
Acute myeloid leukemia (AML) is a disease with a poor prognosis including a 5-year overall
survival (OS) of app. 20% for the entire population. In particular, the outcome of elderly
patients with AML is dismal and the majority of patients die within the first year after
diagnosis. This is also because treatment options for elderly patients with AML significantly
differ from patients of younger age. In fact, comorbid conditions are common among the
elderly such as heart disease, renal insufficiency and vascular disease thus influencing the
ability to withstand intensive therapy. Elderly patients are also more likely than younger
patients to develop severe, life threatening infections during the course of treatment. In
addition to infectious complications, hemorrhages due to severe thrombocytopenia are
responsible for morbidity and mortality in a considerable amount of patients. Compared with
younger AML patients, elderly individuals with AML display a higher incidence of
poor-prognosis karyotypes, of a preceding myelodysplastic syndrome (MDS), and greater
expression of proteins involved in intrinsic resistance to chemotherapeutic agents. As a
result conventional anthracycline based chemotherapy is only infrequently used in patients
above the age of 65 years. Based on a recent randomized trial (Kantarjian et al. 2012)
low-intensity epigenetic therapy with decitabine (DAC) has become the first-line standard of
care in most European countries including Germany. Nevertheless, even with this treatment the
1-year OS is approximately 30 % only. Furthermore, severe thrombocytopenia is a main side
effect of this therapy and can prevent adequate continuation of treatment being crucially for
treatment success. Supportive care with platelet transfusions is effective primarily only
over short periods and often requires hospitalization and therefore lowers the quality of
life of these patients in their palliative situation. Therefore, patients could benefit from
an approach aiming at an increase of platelet counts through combined use of DAC with an oral
thrombopoietin receptor agonist like eltrombopag (EPAG). This could allow for a better
adherence to DAC therapy by preventing dose delays due to prolonged thrombocytopenia.
Additionally, the potential antileukemic effect of EPAG could also be beneficial for these
AML patients.