Study Impact on Outcome of Eltrombopag in Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy

A Phase II Randomized Placebo-controlled Study to Assess the Impact on Outcome of Eltrombopag Administered to Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy

Phase II randomized placebo-controlled study to assess the impact on outcome of Eltrombopag administered to elderly patients with Acute Myeloid Leukemia (AML) receiving induction chemotherapy. A phase II multicenter and randomized placebo-controlled study

Subjects will be randomized 1:1 to receive Eltrombopag or matching placebo, in double blinded.

To compare overall survival rate at 12 months between the two arms, with or without 200 mg of Eltrombopag daily after induction chemotherapy

Arm A : Eltrombopag 200 mg (100 mg/day for east Asian heritage) once daily from day 11 of induction chemotherapy to AML response evaluation or platelets count > 100 x 10 Giga/L (maximum day 45)

Arm B : Placebo once daily from day 11 of induction chemotherapy to AML response evaluation or platelets count > 100 x 10 Giga/L. (maximum day 45)

Inclusion Criteria

• 60 years of age.

• AML de novo, except AML 3 and AML 7.

• AML with no adverse cytogenetic according to Medical Research Council (MRC) 2010 classification.

• Subjects should be eligible for intensive chemotherapy by Daunorubicine, cytarabine, Lomustine.

• Eastern Cooperative Oncology Group (ECOG) < 3 (appendix 1).

• SORROR ≤ 3 (appendix 2).

• Adequate baseline organ function defined by the criteria below:

  • Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) range except cases clearly not indicative of inadequate liver function
  • Alanine Aminotransferase (ALAT) and Aspartate Aminotransferase (ASAT) ≤ 3 x ULN
  • Creatinin ≤ 1.5 x ULN

• Adequate cardiac function with Left Ventricular Ejection fraction (LVEF) ≥50%

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

• Women will be menopausal to be enrolled

• The patient must give written (personally signed and dated) informed consent before completing any study-related procedure which means assessment or evaluation that would not form part of the normal medical care of the patient and before the start of induction chemotherapy.

• Affiliated to the French Social Security (Health Insurance).

Exclusion criteria

• Subjects with a diagnosis of acute promyelocytic (M3) or megakaryocytic leukemia (M7).
• AML with adverse cytogenetic according to the MRC 2010 classification.
• AML secondary to Myelodysplastic syndrome (MDS), Myeloproliferative neoplasm (MPN)
• Clinical symptoms suggesting active central nervous system leukemia, or presence of extramedullary AML.
• Previous exposure to anthracycline.
• Previous AML treatment other than hydroxyurea.
• Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the first dose of study medication.
• History of thromboembolic event or other condition requiring ongoing use of anticoagulation either with warfarin or low molecular-weight heparin.
• History of another malignancy within the past three years except basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association (NYHA) Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block).
• Patient requiring platelets transfusion with platelets > 10 x 10 Giga/L, for whatever reason.
• History of treatment with romiplostim or other Thrombopoietin receptor (TPO-R) agonists.
• Uncontrolled active infection.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent.
• Known active HIV, Hepatitis B or C infection.
• Pregnancy or breastfeeding.