Study of Efficacy and Safety of Eltrombopag in Patients With Poor Graft Function
Condition: Poor Graft Function
Intervention: Eltrombopag
Intervention description: Eltrombopag was provided as 50 mg or 25 mg film-coated tablets for oral use administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Eltrombopag; Hematological response; Poor graft function; Stem cell transplantation; Adult; ELTION; Phase II

Summary:

      The purpose of this study was to evaluate the efficacy of eltrombopag for poor graft function
      (PGF) on overall hematologic response (partial and complete), as determined by platelet,
      hemoglobin and neutrophil counts by 16 weeks after the initiation of eltrombopag in patients
      with poor graft function after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient must be able to understand and communicate with the investigator and comply
             with the requirements of the study and must provide written, signed and dated informed
             consent form before any study assessment is performed

          2. Male of female patients ≥ 18 years of age

          3. Patients diagnosed with primary or secondary poor graft function (PGF) defined as two
             or more cytopenias after day +30 post-transplant (re-tested in a peripheral blood
             analysis at screening):

               1. Platelet count <20,000/ µL (mandatory)

               2. Absolute neutrophil count (ANC) <1,000/µL

               3. Hemoglobin <100 g/L

          4. Presence of donor chimerism >90% in screening visit

          5. Karnofsky status ≥90% (Karnofsky assessment must be performed within 7 days prior to
             Day 1)

        Exclusion Criteria:

          1. Pregnant or nursing (lactating women).

          2. Evidence of active acute or chronic graft versus host disease (GVHD).

          3. Evidence of any active malignancy.

          4. Subjects who are human immune deficiency virus (HIV), hepatitis C virus (HCV),
             hepatitis B surface antigen (HBsAg) positive in screening visit.

          5. Cytogenetic abnormality in chromosome 7 present before the allo-HSC.

          6. Evidence of any clonal abnormality on cytogenetics (in bone marrow analysis).

               -  A local post-transplant conventional cytogenetic assessment should be available
                  within 8 weeks before Day 1.

               -  If the cytogenetics is not valuable, i.e, it does not show metaphases, a FISH for
                  MDS-related most frequent abnormalities including chromosome 7 is accepted.

             As a consequence, patients with dry tap bone marrow aspiration are NOT eligible.

          7. Evidence of bone marrow involvement or progression of the underlying disease assessed
             by the applicable methods in each case.

          8. Evidence of thrombotic microangiopathy.

          9. Evidence of possible causes of cytopenia other than PGF (active infections, myelotoxic
             drugs, hypersplenism…).

         10. Prior use of any thrombopoietin receptor (TPO-R) agonists for PGF.

         11. AST or ALT levels >3 x ULN.

         12. Creatinine level ≥1.5 x ULN.

         13. Total bilirubin level ≥1.5 x ULN.

         14. Previous thromboembolic event (other than line-related upper extremity thrombosis)

         15. Hypersensitivity to eltrombopag or its components.

         16. Clinically significant ECG abnormality history or current diagnosis of cardiac disease
             indicating significant risk of safety for subjects participating in the study such as
             uncontrolled or significant cardiac disease or impaired cardiac function including any
             of the following:

               1. . Corrected QTc > 450 msec (male subjects), > 460 msec (female subjects) using
                  Fredericia correction (QTcF) on the screening ECG

               2. . Myocardial infarction

               3. . Uncontrolled congestive heart failure

               4. . Unstable angina

               5. . Congenital long QT syndrome.

         17. Administration of an investigational drug within 30 days or 5 half-lives, whichever is
             longer, preceding the first dose of study treatment.

         18. Patient with liver cirrhosis.

         19. Risk factors for Torsade de Pointes including uncorrected hypokalemia or
             hypomagnesemia.

         20. Subjects with any serious and/ or unstable pre-existing medical, psychiatric disorder
             or other conditions that could interfere with patient´s safety, obtaining informed
             consent or compliance with the study procedures as per investigator discretion.