Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy
Condition: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Myelodysplastic Syndromes; Hypereosinophilic Syndrome
Intervention: eltrombopag olamine
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well eltrombopag olamine works in improving the recovery of
      platelet counts in older patients with Acute Myeloid Leukemia (AML) undergoing induction (the
      first treatment given for a disease) chemotherapy. Platelet counts recover more slowly in
      older patients, leading to risk of complications and the delay of post-remission therapy.
      Eltrombopag olamine may cause the body to make platelets after chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All categories of AML will be included except for acute promyelocytic leukemia (APL),
             acute megakaryocytic leukemia, and acute leukemias of ambiguous lineage 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 [World Health Organization] classification), chronic myelomonocytic
             leukemia (CMML); therapy-related AML and those with a prior autologous hematopoietic
             cell transplantation are eligible.

          -  No morphological evidence of disease on day 14 bone marrow examination following IC

          -  Must be able to give voluntary informed written consent to participate in the study;
             informed consent will be obtained prior to initiation of remission IC 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:

               1. 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.

               2. 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
             disease (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/MPN neoplasm, unclassifiable will be
             excluded. AML patients with presenting features suspicious of underlying unrecognized
             MPD such as marked splenomegaly (> 20 cm) and 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 12 months prior to signing informed consent. 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).

          -  Evidence of fibrosis on bone marrow examination at the time of diagnosis

          -  Active participation in any other investigational treatment study

          -  Uncontrolled intercurrent illness including, but not limited to uncontrolled
             infection, symptomatic congestive heart failure, cardiac arrhythmia, unstable angina
             or renal insufficiency (acute or chronic) on hemodialysis

          -  Liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT])
             can not be greater than or equal to 2.5 times the upper limits of normal (ULN)

          -  Total bilirubin ≥ 1.5 x ULN within 14 days of enrollment.

          -  Serum creatinine should be ≥ 2.5 x ULN within 14 days of enrollment

          -  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)

          -  Known history of human immunodeficiency virus (HIV) or active hepatitis B or C

          -  No major surgery within 2 weeks prior to trial enrollment

          -  Female subject is pregnant 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.