A Safety and Efficacy Study of Eltrombopag in Subjects With AML
Condition: Acute Leukaemia
MeSH terms: Leukemia
Intervention: Daunorubicin; Cytarabine; Eltrombopag; Placebo
Intervention description: For subjects between the ages of 18 and 60 years, 90 mg/m2/day by bolus IV injection through a freshly established free-flowing IV line for 10-15 minutes on days 1, 2, and 3. For subjects > 60 years: daunorubicin dose was adjusted to 60mg /m2.; 100 mg/m2/day continuous IV infusion on Days 1 through 7.; 200 mg orally, once daily, beginning on Day 4 of the first cycle of induction. After 7 days, the dose of the Investigational Product (IP) was to be increased to 300 mg if platelet counts were <100 Gi/L. IP continued until achievement of platelet count of at least 200 Gi/L or assessment of remission of bone marrow status or a maximum of 42 days after initiation of most recent induction. In subjects of East Asian heritage 100 mg orally once daily (a 50% dose reduction) was used and after 7 days, the dose of IP was increased to 150 mg if platelet counts were <100 Gi/L.; Orally, once daily, beginning on Day 4 of the first cycle of induction. After 7 days, the dose given was matching 300 mg Eltrombopag if platelet counts were <100 Gi/L. Placebo continued until achievement of platelet count of at least 200 Gi/L or assessment of remission of bone marrow status or a maximum of 42 days after initiation of most recent induction. In subjects of East Asian heritage placebo matching 100 mg Eltrombopag orally once daily was used and after 7 days, the placebo matching 150 mg Eltrombopag was given if platelet counts were <100 Gi/L.
Intervention MeSH terms: Cytarabine; Daunorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 148.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: AML; de novo AML; leukemia; sAML/MDS; acute myeloid leukemia; acute myelogenous leukemia (AML); secondary acute myeloid leukemia; ETB115; Eltrombopag; thrombocytopenia; oral thrombopoietin receptor agonist

Summary:

      The purpose of this randomized, blinded, placebo-controlled study was to provide clinical
      safety and exploratory efficacy data on the use of Eltrombopag in adult subjects with Acute
      Myeloid Leukemia (AML) receiving standard induction chemotherapy with daunorubicin plus
      cytarabine. A minimum of 120 evaluable subjects newly diagnosed with AML was stratified by
      antecedent malignant hematologic disorder and age.
    

Eligibility criteria:

        Inclusion Criteria

          -  Age >=18 years

          -  Diagnosed with AML according to the WHO 2008 classification. Note: subjects with
             secondary AML following Myelodysplastic syndrome or secondary to previous leukemogenic
             therapy are allowed provided that a record of previous MDS history or leukemogenic
             therapy history is available.

          -  Eligible for induction by daunorubicin + cytarabine.

          -  Eligible to give informed consent to participate in the study.

          -  Have adequate baseline organ function defined by the following criteria:

        Total bilirubin <=1.5 x upper limit of normal (ULN) except for Gilbert's syndrome, or other
        conditions that are not indicative of inadequate liver function (i.e. elevation of indirect
        bilirubin (haemolytic) in the absence of alanine aminotransferase [ALT] abnormality).

        ALT <=3 x ULN. Serum Creatinine <=2.5 x ULN.

          -  Adequate cardiac function with LVEF >=50% as assessed by echocardiogram (ECHO) or
             Multi Gated Acquisition Scan (MUGA.

          -  Subjects with a QT interval corrected for heart rate according to Bazett's formula
             (QTcB) <450millisecond (msec) or <480msec for subjects with bundle branch block. The
             QTc should be based on single or averaged QTc values of triplicate electrocardiograms
             (ECGs) obtained over a brief recording period.

          -  Women must be either of non-childbearing potential or women with child-bearing
             potential and men with reproductive potential must be willing to practice acceptable
             methods of birth control during the study.

          -  Men with a female partner of childbearing potential must have either had a prior
             vasectomy or agree to use effective contraception from time of randomization until 30
             days after the last dose of investigational product.

          -  Women of childbearing potential must have a negative serum pregnancy test within 7
             days of first dose of study treatment and agree to use effective contraception during
             the study and for 30 days following the last dose of investigational product.

        Exclusion Criteria

          -  A diagnosis of acute promyelocytic (M3) or acute megakaryocytic leukaemia (M7).

          -  Previous history of exposure to an anthracycline compound.

          -  Previous AML treatment (other than hydroxyurea).

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that, in
             the view of the treating physician, would place the participant at an unacceptable
             risk if he or she were to participate in the study or would prevent that person from
             giving informed consent.

          -  History of thromboembolic event or other condition requiring ongoing use of
             anticoagulation either with warfarin or low molecular-weight heparin. Note: Occlusion
             of a central line is not exclusion.

          -  Treatment with an investigational drug within 30 days or 5 half lives, whichever is
             longer, preceding the first dose of study medication.

          -  Current and continued use during study treatment period of known Breast cancer
             resistance protein (BCRP) inhibitors or known P-gp inhibitors.

          -  Known active hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection.

          -  Known hypersensitivity to any of the study drugs or its excipients.