Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia

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.