Acute Myeloid LeukemiaPhase 1NCT03197714
Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
A Phase 1 study testing OPB-111077 in people with Acute Myeloid Leukemia, run by Hospital Universitario 12 de Octubre at 6 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- OPB-111077
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 6 sitesSpain
- Study dates
- 7 Sep 2017to 31 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients at least 18 years old.
- Patients diagnosed of non M3 acute myeloid leukemia in relapse after intensive chemotherapy.
- Patients with a highest sensitivity (higher 70% of the samples analyzed) in the bone marrow analysis of the OPB-111077 ex-vivo sensitivity test.
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Hospital San Pedro Alcántara
Cáceres, Extremadura, 10003
MD Anderson Cancer Center
Madrid, 28033
Hospital 12 Octubre
Madrid, 28041
Hospital Universitario Madrid Sanchinarro
Madrid, 28050
Hospital Virgen del Rocío
Seville, 41013
Hospital Universitario La Fe
Valencia, 46026
About this study
Official title: Phase Ib Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
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.
Read more
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.
Patients will be selected and included in the study after testing the response to the drug with the Vivia Biotech ex vivo CDx PharmaFlow PM test. PharmaFlow PM test is a companion diagnostic (CDx) tool that provides a complete pharmacological profile for each individual, allowing the detection of patients resistant to OPB-111077 and enriching the study in patients that respond to the drug. The third of patients more sensitive to OPB-11077 wil be included in the study.
Read the 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. 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- OPB-111077
- Keywords
- Myeloid Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPB-111077Drug
Two dose schemas will be employed:
- Level 1: 200 mg daily
- Level 2: 250 mg daily
| Study group | Role | What they receive |
|---|---|---|
| OPB-111077 | Experimental | Level 1: 200 mg daily Level 2: 250 mg daily Receives: Drug: OPB-111077 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT) of OPB-111077 in patients with in acute myeloid Leukemia.
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.
Measured: 28 days
Secondary outcomes (6)
Overall response rate.
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.
Measured: Up to 8 months
Overall response rate according to IC50
Percentage of patients to reach overall response rate according to IC50.
Measured: Up to 8 months
Overall response rate according to Area under de Curve
Percentage of patients to reach overall response rate according to area under the curve.
Measured: Up to 8 months
Incidence of Treatment-Emergent Adverse Events
Number of events per patient according to NCI CTCAE vs 4.03
Measured: Up to 8 months
Progression Free Survival
Time from the date of informed consent form to the date of progression or death (from any cause), whichever occurs first
Measured: Up to 8 months
Overall Survival
Time from the date of informed consent form to the date of death due to any cause
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2017
- Study start7 Sep 2017
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase Ib, open-label, dose-escalation clinical trial to evaluate the best-tolerated doses in AML relapsed or refractory to chemotherapy
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario 12 de Octubre
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka Pharmaceutical Co., Ltd., Apices Soluciones S.L., Vivia Biotech
- Responsible party
- Principal investigator, Joaquín Martínez López, MD, PhD, Hospital Universitario 12 de Octubre
- Investigators
- Joaquín Martínez López, MD, Principal investigator, Hospital 12 Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03197714
- Sponsor's protocol ID
- FDO-LMA-2016-01
- Other IDs
- 2016-004135-21, 2016
- Status last verified
- Feb 2021
- First submitted
- 13 Jun 2017
- Last updated
- 15 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
- ClinicalTrials.gov ID
- NCT03197714
- Acronym / sponsor ID
- FDO-LMA-2016-01
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Hospital Universitario 12 de OctubreUniversity, hospital or other
- Collaborators
- Otsuka Pharmaceutical Co., Ltd., Apices Soluciones S.L., Vivia Biotech
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 23 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Patients will be selected and included in the study after testing the response to the drug with the Vivia Biotech ex vivo CDx PharmaFlow PM test. PharmaFlow PM test is a companion diagnostic (CDx) tool that provides a complete pharmacological profile for each individual, allowing the detection of patients resistant to OPB-111077 and enriching the study in patients that respond to the drug. The third of patients more sensitive to OPB-11077 wil be included in the study.
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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase Ib, open-label, dose-escalation clinical trial to evaluate the best-tolerated doses in AML relapsed or refractory to chemotherapy
| Arm | Type | Receives |
|---|---|---|
| OPB-111077 | Experimental | Drug: OPB-111077Level 1: 200 mg daily Level 2: 250 mg daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients at least 18 years old.
- Patients diagnosed of non M3 acute myeloid leukemia in relapse after intensive chemotherapy.
- Patients with a highest sensitivity (higher 70% of the samples analyzed) in the bone marrow analysis of the OPB-111077 ex-vivo sensitivity test.
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OPB-111077Two dose schemas will be employed: * Level 1: 200 mg daily * Level 2: 250 mg daily | Drug | OPB-111077 |
Primary outcome
Dose-limiting toxicity (DLT) of OPB-111077 in patients with in acute myeloid Leukemia.
Time frame: 28 days
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.
6 secondary outcomes
Overall response rate.
Time frame: Up to 8 months
Overall response rate according to IC50
Time frame: Up to 8 months
Overall response rate according to Area under de Curve
Time frame: Up to 8 months
Incidence of Treatment-Emergent Adverse Events
Time frame: Up to 8 months
Progression Free Survival
Time frame: Up to 8 months
Overall Survival
Time frame: Up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joaquín Martínez López, MD principal investigator
Hospital 12 Octubre
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OPB-111077 in people with Acute Myeloid Leukemia, run by Hospital Universitario 12 de Octubre at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) of OPB-111077 in patients with in acute myeloid Leukemia. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2021.