SOAR Trial Interventional phase II single-arm study to assess efficacy and safety of Eltrombopag combined with cyclosporine as first line therapy in adult patients with severe acquired aplastic anemia.

The standard of care for the treatment of aplastic anemia patients who are not
candidate for HSCT was immunosuppressive treatment (IST) for a long time.
There are several limitations of IST in severe aplastic anemia (SAA), e.g. the
majority of the responses observed following initial IST are partial with only
a few patients achieving normal blood counts, 1/3 of patients are refractory to
initial IST, hematologic relapses occur in 35% of responders following initial
response to IST, among relapsed patients chronic use of cyclosporine A is not
infrequent which often leads to toxicities and clonal evolution is still
observed in 10-15% of patients.
In order to address these limitations, efforts to improve initial IST in
treatment-naïve patients with the addition of mycophenolate mofetil and
sirolimus to standard horse anti-thymocyte globulin/cyclosporine A (h-ATG/CsA)
or use of lymphocytotoxic agents have not yielded the expected better outcomes
when compared to standard (h-ATG/CsA).
The most important advance in SAA in the recent years has been the seminal
observation that a thrombopoietin receptor agonist, eltrombopag, has activity
in SAA.
The lack of availability of anti-thymocyte globulin (ATG) in several countries
has left a large proportion of patients with SAA with limited treatment options
and poor outcome. In this context, the combination of cyclosporine and
eltrombopag, 2 therapies with different modes of action, is an attractive
therapeutic option to address this unmet medical need.
The main objective of this study is to assess the safety and efficacy of
eltrombopag and cyclosporine in outpatient setting for the treatment-naïve SAA
patients mainly in countries where h-ATG is not available.

Primary:
To evaluate the efficacy of eltrombopag + cyclosporine as first-line therapy on
overall hematologic response (neutrophil, platelet, hemoglobin) by 6 months.
Secondary:
Overall hematologic response (neutrophil, platelet, hemoglobin) by 3 and 12
months, duration of hematologic response, disease relapse rate, clonal
evolution, need for and independence of blood and platelet transfusion, overall
survival, symptoms and quality of life, safety and tolerability,
pharmacokinetics.

interventional phase II, single-arm, multicenter, open-label, study to
investigate the efficacy and safety of the combination of eltrombopag and
cyclosporine in treatment-naive patients with SAA as first line therapy
administered for 6-months
a follow-up for up to 24 -months of all patients who responded and not
responded at month 6
Responders will receive cyclosporine only, up to 24 months with a taper
regimen. After which EOS will take place for safety reasons.
Non-responders will stop eltrombopag and cyclosporine after 6 months,
cyclosporine will be stopped for non-responders in 2nd part from 6-24 months
Approx. 50 patients.

Treatment with eltrombopag and cyclosporine.

Risk: Adverse effects of eltrombopag in combination with cyclosporine and
cyclosporine alone.
Burden: Screening 2 weeks, treatment with eltrombopag and cyclosporine 6
months, treatment with alone cyclosporine 18 months. safety visits 30days after
last treatmen
40 visits in 2 years. Duration mostly 1-2 hours.
Physical examination: 6 times.
Blood tests (20 ml/occasion): every visit; 1 day with 8 h PK measurements with
5 blood draws.
Pregnancy test (if relevant): every 3-4 weeks, to be conducted partly at home.
Bone marrow sample:4 times.
ECG: max5 times.
Questionnaires: FACIT-Fatigue, FACT-TH18, EQ-5D-5L: 12 times.
Eye examination : 5 times.
Neurological examination : 5 times.
Optional storage and use of the remaining blood and tissue for future research.