Eltrombopag Olamine in Improving Platelet Recovery in Older Patients with Acute Myeloid Leukemia Undergoing Chemotherapy

Inclusion Criteria

• All categories of AML will be included except for acute promyelocytic leukemia (APL) (AML-M3 as defined by 1976 French-American-British [FAB] classification, or APL with t(15;17)(q22;q12); PML-RARA as defined by the revised 2008 World Health Organization [WHO] classification of myeloid neoplasms and acute leukemias), acute megakaryocytic leukemia (AML-M7 type as per FAB or AML [megakaryoblastic] with t(1;22)(p13;q13); RBM15-MKL1 as per WHO 2008 revised classification) and acute leukemias of ambiguous lineage (as per WHO 2008 revised classification), undergoing 7 + 3 remission IC with cytarabine and an anthracycline (daunorubicin or idarubicin); all cases have to be histopathologically confirmed by a diagnostic bone marrow biopsy; use of granulocyte colony-stimulating factor (G-CSF) for any indication must have been discontinued at least 7 days prior to entry into the study
• Patients with secondary AML arising out of myelodysplastic syndrome (MDS) (all subtypes under WHO classification), chronic myelomonocytic leukemia (CMML); therapy-related AML and those with a prior autologous hematopoietic cell transplantation are eligible
• No morphological evidence of disease (defined as marrow myeloblast percentage of < 5% and/or documentation from hematopathologist indicating no morphological evidence of leukemia) on day 14 bone marrow examination (range, day 14-17; day 1 refers to the first day of IC) following remission IC
• Must be able to give voluntary informed written consent to participate in the study; informed consent will be obtained prior to starting of remission IC (can be obtained even on the first day of remission IC if obtained before administration of chemotherapy) and before any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment; all men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below: * Females of childbearing potential: recommendation is for 2 effective contraceptive methods during the study; adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation * Male patients with female partners who are of childbearing potential: recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study or to abstain
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Exclusion Criteria

• 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
• Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 12 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer)
• Secondary AML arising out of myeloproliferative neoplasms (as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias) and MDS/myeloproliferative (MPD) neoplasms other than CMML (as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias); refractory anemia with ringed sideroblasts with thrombocytosis (RARS-T) classified as MDS/myeloproliferative neoplasm (MPN) neoplasm, unclassifiable will be excluded; AML patients with presenting features suspicious of underlying unrecognized MPD such as marked splenomegaly (>= 20 cm) and or thrombocytosis (> 400,000 per microliter) will be excluded; patients with relapsed or refractory AML will be excluded
• Radiation therapy, cytotoxic chemotherapy, and combined modality (both radiation and chemotherapy) used to treat other cancers or medical conditions and administered within 6 months prior to study enrollment; use of hydroxyurea or emergent leukapheresis (for cytoreduction of highly elevated white blood cell counts) is permissible; those AML patients who initially receive treatment with all-trans retinoic acid (ATRA) for presumptive diagnosis of APL but if APL is ruled out in final pathology will be eligible for the study
• Prior history of treatment with recombinant thrombopoietin (TPO) or TPO-receptor (R) agonists
• History of arterial or venous thrombosis (excluding line-thrombosis) within the last 1 year, or those with known inherited coagulopathies; arterial or venous thrombosis includes pulmonary embolism, deep vein thrombosis of both upper (excluding line-thrombosis) and lower extremities, coronary artery disease managed medically or requiring intervention (percutaneous stent placement or coronary bypass surgery), cerebrovascular accident (for transient ischemic attacks clinical documentation is required), or involvement of other organs (such as hepatic, renal, spleen or other sites)
• Any evidence of fibrosis on morphological examination of bone marrow at the time of AML diagnosis
• Concomitant participation in any other investigational treatment study; simultaneous participation in non-therapeutic or observational studies will not be an exclusion criterion
• Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic or decompensated congestive heart failure, cardiac arrhythmia, unstable angina, cirrhosis or renal insufficiency (acute or chronic) on hemodialysis (at the time of diagnosis of AML)
• Liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= 3.5 times the upper limits of normal (ULN) 14 days prior to study enrollment
• Total bilirubin >= 3.5 x ULN on the start day of eltrombopag unless considered due to Gilbert’s disease
• A known immediate or delayed hypersensitivity reaction or idiosyncrasy that, in the opinion of the Medical Monitor is due to drugs chemically related to eltrombopag or excipients (e.g. mannitol)
• No known history of human immunodeficiency virus (HIV) or active hepatitis B or C
• No major surgery within 2 weeks prior to signing of study enrollment
• Pregnancy or breast feeding
• Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment