The optimal management of relapsed AML in patients who are not candidates for HSCT has yet to
      be delineated. Given the median age at which AML is diagnosed and the high incidence of
      relapse and significant toxicities associated with standard intensive remission induction
      chemotherapy, new treatment options are needed to optimize AML outcomes. Changes on
      metabolism are critical in Acute Myeloid Leukaemia (AML); besides, leukemic cells have high
      requirements of energy and high basal metabolism. For this reason we hypothesized that
      deregulations of energy metabolism and mitochondria could play a central role in AML.
      OPB-111077, a novel low-molecular-weight compound discovered by Otsuka Pharmaceutical Co,
      Ltd, is a new class drug targeting cancer cell metabolisms and STAT3 and is being developed
      as an orally active antitumor agent for the treatment of various cancers. Sufficient
      preclinical studies have shown its activity in several types of tumors and especially in AML.
      Although in a phase I study their activity has been small in a group solid tumor, we may
      hypostatize that this drug could be more efficient in tumor cells with a high proliferative
      index as AML.

      This is an open-label, phase Ib dose-escalation clinical trial to evaluate the safety and
      tolerability of oral OPB-111077 in AML relapsed or refractory to chemotherapy patients.
      OPB-111077 will be administered orally on a once daily dose schedule.

      This open-label, nonrandomized trial will comprise 2 stages. A dose escalation stage will
      characterize the safety, tolerability and MTD, of OPB-111077. Subsequently, an expansion
      stage will further evaluate the safety and antitumor activity of OPB-111077 in AML relapsed
      or refractory to chemotherapy. The overall response rate of OPB-11077 in acute myeloid
      leukemia and its correlation with the ex-vivo PharmaFlow PM test will be also assessed.

      Enrollment to the expansion cohort will begin following determination of the MTD.

      OPB-111077 recommended dose for expansion cohort will be defined during the phase I as MTD.
      Intra patient dose escalation is not allowed at any time of the study.

      Patients will be included in the study upon signed informed consent and will follow study
      procedures.

      Two dose schemas will be employed:

        -  Level 1: 200 mg daily

        -  Level 2: 250 mg daily The starting dose level of oral OPB-111077 will be 200 mg od. A 3
           + 3 dose-escalation scheme will be used.

      A minimum of 3 patients will be initially enrolled per cohort. DLTs will be assessed during
      the DLT assessment window of 28 days following the first dose of OPB-111077. Patients who
      withdraw or are withdrawn from the study prior to completing the DLT assessment window for
      reasons other than a DLT will not be considered evaluable for DLT and will be replaced.

      DLTs will be assessed during the DLT assessment window of 28 days following the first dose of
      OPB-111077. Patients who withdraw or are withdrawn from the study prior to completing the DLT
      assessment window for reasons other than a DLT will not be considered evaluable for DLT and
      will be replaced.