Combination of Eltrombopag With Immunosuppressive Therapy in East-Asian Patients With Severe Aplastic Anemia

This study is designed to evaluate the efficacy and safety of eltrombopag when added to r-ATG and CsA in treatment naive East-Asian adult and pediatric patients with SAA.


Eligibility Criteria:
Inclusion Criteria:

* Written study informed consent and (where applicable) assent from the subject, parent, or guardian must be obtained prior to participation in the study.
* Subjects of East Asian ethnicity aged ≥ 6 years old at the time of written informed consent and assent form (if applicable).

SAA characterized by:

* Bone marrow cellularity \< 25%, or 25-50% with \< 30% residual hematopoietic cells and pancytopenia, with at least two of the following parameters in peripheral blood:
* Absolute neutrophil count \< 0.5×109/L
* Platelet count \< 20×109/L
* Absolute reticulocyte count \< 20×109/L
* HSCT is not suitable or available as a treatment option (determined as per local practices or national guidelines), or has been refused by subject.

Exclusion Criteria:

* Prior IST with any ATG/ALG , alemtuzumab, high dose cyclophosphamide (≥ 45 mg/kg/day), CsA within 6 months, or prior thrombopoietin receptor agonists.
* Eastern Cooperative Oncology Group (ECOG) performance status (age ≥ 16 years) \>2, or Lansky performance status (age \< 16 years) \<50.
* Prior and/or active medical history of:
* Known underlying congenital/inherited bone marrow failure or aplastic anemia (e.g.,such as but not limited to Fanconi anemia, congenital dyskeratosis, congenital amegakaryocytic thrombocytopenia, or Shwachman-Diamond Syndrome)
* Symptomatic paroxysmal nocturnal hemoglobinuria (PNH) and/or PNH clones \>50% of polymorphonuclear neutrophil (PMN) or RBC at time of enrollment Myelodysplastic syndrome (MDS)
* Any cytogenetic abnormalities on karyotyping or FISH within 30 days of study enrollment (an evaluable karyotyping with at least 10 metaphases is mandatory for eligibility)
* Other known or suspected underlying primary immunodeficiency
* Any concomitant malignancies that have not fully recovered from treatment or have not been disease-free for 5 years
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times the upper limit of normal (ULN).
* Creatinine ≥ 2.5×local ULN
* Past medical history of thromboembolism within 6 months, and/or prior or current antiphospholipid antibody syndrome (APS).
* Presence of clinically active uncontrolled significant (of such severity that it would preclude the subject's ability to consent, be compliant with study procedures, tolerate protocol therapy) infection, including bacterial, fungal, mycobacterial, parasitic or viral infection, or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol
* Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks or compromise compliance with the protocol, such as:
* Known hepatocellular disease (e.g. active hepatitis or cirrhosis)
* Impairment of gastrointestinal (GI) function or gastrointestinal disease that may significantly alter the absorption of study treatment (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
* Active skin, mucosa, ocular or GI disorders of Grade \> 1
* Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening. A positive serology for Hepatitis B (HB) is considered as a positive test for HBsAg. In addition, if serology is negative for HBsAg but hepatitis B core antibody (HBcAb) is positive (regardless of hepatitis B surface antibody (HBsAb) status), a hepatitis B virus (HBV) DNA test will be performed and if positive the patient will be excluded.
* Cardiac disorder (subjects with congestive heart disease of New York Heart Association (NYHA) functional classification Grade II/III/IV (for pediatric subjects, refer to the Grade II/III/IV of Modified ross heart failure classification for Children) should not be enrolled; subjects with NYHA Grade II due to cardiac disorder should not be enrolled but those with NYHA Grade II due to aplastic anemia (AA) may be enrolled.), arrhythmia with a risk of thrombosis (e.g. atrial fibrillation), pulmonary hypertension, or uncontrolled hypertension (\>180/100 mmHg).

Other protocol-defined Inclusion/Exclusion may apply.