Eltrombopag and Cyclosporine as First-Line Therapy in Patients with Severe Acquired Aplastic Anemia: A Two-part, 5-year, Single-Arm, Multicenter, Open-label, Phase 2 Trial (SOAR)

Context: Eltrombopag (EPAG), a thrombopoietin receptor agonist (TPO-RA), has shown promising results in severe aplastic anemia (SAA), as a single agent in immunosuppressive therapy (IST)-refractory patients and in treatment-naïve patients when combined with horse antithymocyte globulin (hATG) and cyclosporine (CsA). hATG is unavailable in most parts of the world and is associated with increased toxicity, especially in patients aged >60 years. Moreover, ∼1/3rd of patients after ATG/CsA are considered refractory. Objective: To evaluate the efficacy and safety of EPAG+CsA in outpatient setting for the treatment-naïve patients with SAA mainly in countries where hATG is unavailable. Design: Phase 2, open-label, single-arm, 2-stage study (ClinicalTrials.gov NCT02998645). Eligibility: Patients aged ≥6 years with SAA who had no prior IST treatment with CsA, alemtuzumab, rabbit ATG or hATG, or TPO-RAs. Interventions: EPAG will be administered at 150 mg/day, fixed dosage (and a reduced dosage in patients of Asian ancestry and patients aged 6-11 years), with CsA (administered twice daily) at an initial dose of 10 mg/kg/day to be titrated to obtain a therapeutic trough level of 200–400 μg/L. After 6 months, EPAG treatment will be stopped in all patients and CsA treatment will be continued on a taper regimen in responders. Methods: The primary endpoint is overall hematologic response (complete response [CR]+partial response [PR]) by 6 months (Table 1). The study is planned to enroll ∼50 patients, which will provide>94% probability of a positive signal (≥15 responders) if the true response rate is ≥40%. The key secondary endpoints include safety assessments; overall hematologic response by 3 and 12 months; and overall survival with a follow-up to 5 years (Table 2). Results: Eleven countries (Brazil, France, Hong Kong, Hungary, India, Italy, Korea, Mexico, Netherlands, Spain, Turkey) are involved under European commission/health authority submission process. First patient first visit was on May 11, 2017. Currently, 2 patients were screened and none were enrolled. Recruitment is expected to be completed by August 2018 (from 21 committed sites). Conclusion: This prospective multicenter study will help to determine the role of EPAG+CsA as an outpatient regimen for the first-line treatment in naive patients with SAA. [Formula presented] [Formula presented]