Clinical Trials Logo

Clinical Trial Summary

Phase Ib, open-label, dose-escalation clinical trial to evaluate the best-tolerated doses in Acute Myeloid Leukaemia (AML) relapsed or refractory to chemotherapy.

This open-label, nonrandomized trial will comprise 2 stages. A dose escalation stage will characterize the safety, tolerability and maximum tolerated dose (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.

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

Approximately 6-12 patients will be included in the phase I part of this clinical trial.

Additional patients will be included in the expansion cohort up to a total of 15 patients. The expansion cohort will serve to further evaluate safety simultaneously with preliminary efficacy.


Clinical Trial Description

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.

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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03197714
Study type Interventional
Source Hospital Universitario 12 de Octubre
Contact Joaquín Martínez López, MD
Phone +34 917792787
Email jmartinezlo1967@gmail.com
Status Recruiting
Phase Phase 1
Start date September 7, 2017
Completion date December 2018

See also
  Status Clinical Trial Phase
Recruiting NCT03224819 - Study of AMG 673 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia Early Phase 1
Active, not recruiting NCT02485535 - Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant Phase 1
Recruiting NCT02882321 - Study of IACS-010759 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Phase 1
Recruiting NCT03214562 - Study of the BCL-2 Inhibitor Venetoclax in Combination With Standard Intensive Acute Myeloid Leukemia (AML) Induction/Consolidation Therapy With FLAG-IDA in Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML) Phase 1/Phase 2
Recruiting NCT03298984 - Ph I Study of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML). Phase 1
Not yet recruiting NCT03589729 - Dexrazoxane Hydrochloride in Preventing Heart-Related Side Effects of Chemotherapy in Participants With Blood Cancers Phase 2
Not yet recruiting NCT03454984 - SGI-110 and Donor Lymphocyte Infusions (DLI) After Allogeneic Stem Cell Transplantation Phase 2
Not yet recruiting NCT03603795 - Study Impact on Outcome of Eltrombopag in Elderly Patients With Acute Myeloid Leukemia Receiving Induction Chemotherapy Phase 2
Not yet recruiting NCT03207334 - iCare4: Genomic Signatures With Midostaurin in Acute Myeloid Leukemia (UF-BMT-AML-001) Phase 2
Not yet recruiting NCT03616470 - Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia Phase 3
Not yet recruiting NCT03410407 - Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)
Not yet recruiting NCT03455504 - Venetoclax Add in Combination With Fludarabine, Cyratabine and Idarubicine in Induction for Acute Myelid Leukemia Phase 2
Recruiting NCT03256071 - Low Dose Decitabine + Modified BUCY Conditioning Regimen for High Risk Acute Myeloid Leukemia Undergoing Allo-HSCT Phase 2/Phase 3
Recruiting NCT02668653 - Quizartinib With Standard of Care Chemotherapy and as Maintenance Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML) Phase 3
Recruiting NCT02909972 - Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome Phase 1
Recruiting NCT02975869 - A Collaborative Palliative and Oncology Care Model for Patients With Acute Myeloid Leukemia N/A
Active, not recruiting NCT02899286 - Efficacy and Safety Study of Recombinant Human Arginase 1 in Patients With Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Not yet recruiting NCT02933333 - G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor Phase 4
Recruiting NCT02400255 - Crenolanib Maintenance Following Allogeneic Stem Cell Transplantation in FLT3-positive Acute Myeloid Leukemia Patients Phase 2
Recruiting NCT02543879 - Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies Phase 1