Clinical Trials /

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

NCT03197714

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
  • Official Title: Phase Ib Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia

Clinical Trial IDs

  • ORG STUDY ID: FDO-LMA-2016-01
  • NCT ID: NCT03197714

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
OPB-111077OPB-111077

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
OPB-111077ExperimentalLevel 1: 200 mg daily Level 2: 250 mg daily
  • OPB-111077

Eligibility Criteria

        Inclusion Criteria:

          -  Patients at least 18 years old.

          -  Patients diagnosed of non M3 acute myeloid leukemia in relapse after intensive
             chemotherapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          -  Bilirubin ≤ 2 × Upper Limit of Normal (ULN). For subjects with known Gilbert's
             disease, bilirubin ≤ 3.0 mg/dL.

          -  Serum creatinine ≤2 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min.

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.

          -  Left Ventricular Ejection Fraction (LVEF) must be equal to or greater than 50%.

          -  New York Heart Association (NYHA) congestive heart failure (CHF) class II or better.

          -  Recovery from adverse effects of prior therapy at time of enrollment to ≤ Grade 1
             (excluding alopecia).

          -  Life expectancy ≥3 months

          -  Patients, or appropriate designee, must be able to provide informed consent.

        Exclusion Criteria:

          -  Individuals with a history of other malignancies.

          -  Subject has uncontrolled intercurrent illness that would limit compliance with study
             requirements.

          -  Patients diagnosed of M3/Acute promyelocytic leukemia (APL).

          -  The subject has received systemic antineoplastic therapy within 14 days of study
             treatment.

          -  The subject has received any investigational agent within 28 days before the first
             dose of study treatment.

          -  The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all
             prior therapies except alopecia and other non-clinically significant Adverse Events
             (AEs).

          -  The subject has concurrent uncompensated hypothyroidism or thyroid dysfunction within
             7 days before the first dose of study treatment.

          -  Gastrointestinal disorders particularly those associated with a high risk of
             perforation or fistula formation.

          -  Malabsorption syndrome.

          -  Subject is unable to swallow capsules or tablets.

          -  Subject is pregnant or breastfeeding.

          -  Patients with history of allergic reactions attributed to components of OPB- 111077
             that are not easily managed

          -  Subject has systemic infection requiring IV antibiotic therapy within 7 days preceding
             the first dose of study drug, or other severe infection.

          -  Uncontrolled intercurrent illness that would limit compliance with study requirements.

          -  Patients with serious medical or psychiatric illness likely to interfere with
             participation in this clinical study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity (DLT) of OPB-111077 in patients with in acute myeloid Leukemia.
Time Frame:28 days
Safety Issue:
Description:Any adverse event related to the study drug that occurred during the first cycle and considered relevant: Any Grade 3 or 4 non-hematologic toxicity Any unexpected non-tolerable grade II adverse event possibly related to the treatment regimen that requires delay beyond 1 week until recovery Hematological toxicity is not considered doses limiting due to the characteristic of Acute Myeloid Leukemia.

Secondary Outcome Measures

Measure:Overall response rate.
Time Frame:Up to 8 months
Safety Issue:
Description:Percentage of patients to reach complete remission (CR), morphologic complete remission with incomplete blood count recovery (Cri) or partial remission (PR) according to Cheson et al criteria.
Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:Up to 8 months
Safety Issue:
Description:Number of events per patient according to NCI CTCAE vs 4.03
Measure:Progression Free Survival
Time Frame:Up to 8 months
Safety Issue:
Description:Time from the date of informed consent form to the date of progression or death (from any cause), whichever occurs first
Measure:Overall Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Time from the date of informed consent form to the date of death due to any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hospital Universitario 12 de Octubre

Trial Keywords

  • Myeloid Leukemia

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