LeukemiaPhase 1NCT03404726
A Study to Investigate BAY2402234, a Dihydroorotate Dehydrogenase (DHODH) Inhibitor, in Myeloid Malignancies
A Phase 1 study testing BAY2402234 in people with Leukemia, run by Bayer at 5 sites in 2 countries.
Trial summary
The primary objective is to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), or pharmacological active dose (PAD) of BAY2402234 in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- BAY2402234
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 29 Mar 2018to 26 Jan 2021
- 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 with relapsed or refractory AML. Relapsed AML is defined as relapse after achieving a response to initial therapy and refractory AML is defined as failure to achieve a response after one previous line of therapy. Response is defined as per IWG criteria (CR, CRi or CRp). Patients who are not candidates to receive or who decline standard of care therapy are also eligible.
- Patients with intermediate-1 or higher risk MDS who have failed therapy with a hypomethylating agent, or have failed lenalidomide therapy if harboring a 5q-chromosomal deletion.
- Patients with relapsed/refractory CMML.
- Estimated glomerular filtration rate (eGFR) > 40 mL per 1.73 m^2
- Patients must have adequate coagulation (international normalized ratio [INR] ≤ 1.5; activated partial thromboplastin time [aPTT] ≤1.5 X the upper limit of normal [ULN]; patients on chronic anticoagulation therapy at investigator's discretion; patients on chronic use of direct-acting oral anticoagulants who have acceptable benefit-risk ratio at investigator's discretion)
- Adequate liver function (total bilirubin ≤1.5 X ULN (or ≤3 X ULN in patients with documented Gilbert's syndrome or for patients with hyperbilirubinemia considered due to myeloid disease), alanine aminotransferase [ALT] and aspartate aminotransferase [AST] ≤3 X ULN (or ≤5 X ULN for patients with liver involvement of their myeloid disease)
Who cannot join
- Patients eligible for hematopoietic stem cell transplantation
- Clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia
- Human immunodeficiency virus (HIV) infection
- Chronic or active hepatitis B or C if not controlled by antiviral therapy
- History of organ allograft (allogeneic bone marrow or stem cell transplant) within 3 months prior to first dose of study drug
- Serious, uncontrolled infection requiring systemic antibiotic, antifungal or antiviral therapy. Prophylactic antibiotic, antifungal and/or antiviral therapy is permitted
- Left ventricular ejection fraction (LVEF) <40%
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Montefiore Medical Center
The Bronx, New York, 10467-2490
About this study
Official title: An Open-label, Multicenter Phase 1 Study to Characterize the Safety, Tolerability, Preliminary Antileukemic Activity, Pharmacokinetics, and Maximum Tolerated Dose or Pharmacological Active Dose of BAY2402234 in Patients With Advanced Myeloid Malignancies
The primary objective is to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), or pharmacological active dose (PAD) of BAY2402234 in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML).
The secondary objective is to evaluate evidence of clinical efficacy associated with BAY2402234 in patients with AML (defined as Complete remission, Complete remission with partial hematologic recovery), and MDS (defined as hematological improvement).
- Conditions
- Leukemia
- Being tested
- BAY2402234
- Keywords
- Acute myeloid leukemia, Myelodysplastic Syndromes, Chronic myelomonocytic leukemia, Dihydroorotate dehydrogenase (DHODH) inhibitor
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY2402234Drug
BAY2402234 is a potent and selective small molecule inhibitor of dihydroorotate dehydrogenase. A solution of BAY2402234 will be available to initiate the trial and there are plans to transition to a tablet form of BAY2402234 once it becomes available. Both liquid and tablet formulations of BAY2402234 will be continually administered once daily by mouth in 28 day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Dose escalation with sequential cohorts enrolling patients with AML, MDS, or CMML. Patients will be treated in 28-day cycles with once daily oral administration of BAY2402234 Receives: Drug: BAY2402234 |
| Dose Expansion: AML | Experimental | After completion of dose escalation, an expansion cohort comprised of patients with AML will start. These patients will be treated in 28 day cycles with once daily oral administration of BAY2402234 at the maximum tolerated dose or pharmacologically active dose. Receives: Drug: BAY2402234 |
| Dose Expansion: MDS | Experimental | After completion of dose escalation, an expansion cohort comprised of patients with MDS will start. These patients will be treated in 28 day cycles with once daily oral administration of BAY2402234 at the maximum tolerated dose or pharmacologically active dose. Receives: Drug: BAY2402234 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
The MTD was defined as the maximum dose administered during Cycle 1 at which the estimated dose-limiting toxicity (DLT) probability is closest to 30%.
Measured: Up to 42 days after the first dose
Number of subjects with DLTs
A dose-limiting toxicity (DLT) was defined as any of the events that are clearly unrelated to underlying disease and occurring at any particular dose level during the first 28 days (i.e. Cycle 1) of treatment for non-hematological DLTs, or 42 days after the start of treatment, in the absence of active disease (i.e. < 5% blasts in bone marrow and absence of leukemic blasts in peripheral blood) for hematological DLTs. The National Cancer Institute Common Terminology Criteria for Adverse Events Version (CTCAE) v4.03 will be used to assess toxicities.
Measured: Up to 42 days after the first dose
AUC(0-24) (area under the concentration versus time curve from time zero to 24 hours) after single dose on Cycle 1 Day 1 (C1D1)
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after dose administration at C1D1
Cmax (maximum observed drug concentration in plasma after single dose administration) on C1D1
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours (QD cohorts=until 24 hours; BID cohort=until 12 hours) after dose administration at C1D1
AUC(0-24)md (AUC(0-24) after multiple dose) on Cycle 1 Day 15 (C1D15)
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after dose administration at C1D15
Cmax,md (Cmax after multiple dose) on C1D15
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours (QD cohorts=until 24 hours; BID cohort=until 12 hours) after dose administration at C1D1
Number of subjects with Treatment Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence (i.e. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study.
Measured: From first application of study intervention up to 30 days after end of treatment
Secondary outcomes (2)
Number of acute myeloid leukemia (AML) patients with complete remission (CR) and complete response with partial recovery of peripheral blood counts (CRh)
Measured: Up to 6 months on average
Number of myelodysplastic syndrome (MDS) patients with hematologic improvement (erythroid response, platelet response, and neutrophil response)
Measured: Every month until disease progression or patient was withdrawn from study, up to 6 months on average
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2018
- Study start29 Mar 2018
- Primary completion26 Jan 2021
- Study completion26 Jan 2021
Why it stopped: Lack of sufficient clinical benefit
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03404726
- Sponsor's protocol ID
- 19420
- Other IDs
- 2017-002896-24, 2017
- Status last verified
- Dec 2021
- First submitted
- 29 Nov 2017
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter Phase 1 Study to Characterize the Safety, Tolerability, Preliminary Antileukemic Activity, Pharmacokinetics, and Maximum Tolerated Dose or Pharmacological Active Dose of BAY2402234 in Patients With Advanced Myeloid Malignancies
- ClinicalTrials.gov ID
- NCT03404726
- Acronym / sponsor ID
- 19420
- Conditions
- Leukemia
- Keywords
- Acute myeloid leukemia, Myelodysplastic Syndromes, Chronic myelomonocytic leukemia, Dihydroorotate dehydrogenase (DHODH) inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of sufficient clinical benefit
- Enrolment
- 40 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2018 (actual)
- Primary completion
- 26 Jan 2021 (actual)
- Study completion
- 26 Jan 2021 (actual)
- First posted
- 19 Jan 2018 (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.
The primary objective is to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), or pharmacological active dose (PAD) of BAY2402234 in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML).
The secondary objective is to evaluate evidence of clinical efficacy associated with BAY2402234 in patients with AML (defined as Complete remission, Complete remission with partial hematologic recovery), and MDS (defined as hematological improvement).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: BAY2402234Dose escalation with sequential cohorts enrolling patients with AML, MDS, or CMML. Patients will be treated in 28-day cycles with once daily oral administration of BAY2402234 |
| Dose Expansion: AML | Experimental | Drug: BAY2402234After completion of dose escalation, an expansion cohort comprised of patients with AML will start. These patients will be treated in 28 day cycles with once daily oral administration of BAY2402234 at the maximum tolerated dose or pharmacologically active dose. |
| Dose Expansion: MDS | Experimental | Drug: BAY2402234After completion of dose escalation, an expansion cohort comprised of patients with MDS will start. These patients will be treated in 28 day cycles with once daily oral administration of BAY2402234 at the maximum tolerated dose or pharmacologically active dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with relapsed or refractory AML. Relapsed AML is defined as relapse after achieving a response to initial therapy and refractory AML is defined as failure to achieve a response after one previous line of therapy. Response is defined as per IWG criteria (CR, CRi or CRp). Patients who are not candidates to receive or who decline standard of care therapy are also eligible.
- Patients with intermediate-1 or higher risk MDS who have failed therapy with a hypomethylating agent, or have failed lenalidomide therapy if harboring a 5q-chromosomal deletion.
- Patients with relapsed/refractory CMML.
- Estimated glomerular filtration rate (eGFR) > 40 mL per 1.73 m^2
- Patients must have adequate coagulation (international normalized ratio [INR] ≤ 1.5; activated partial thromboplastin time [aPTT] ≤1.5 X the upper limit of normal [ULN]; patients on chronic anticoagulation therapy at investigator's discretion; patients on chronic use of direct-acting oral anticoagulants who have acceptable benefit-risk ratio at investigator's discretion)
Key exclusion criteria (7 listed)
- Patients eligible for hematopoietic stem cell transplantation
- Clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia
- Human immunodeficiency virus (HIV) infection
- Chronic or active hepatitis B or C if not controlled by antiviral therapy
- History of organ allograft (allogeneic bone marrow or stem cell transplant) within 3 months prior to first dose of study drug
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 |
|---|---|---|
| BAY2402234BAY2402234 is a potent and selective small molecule inhibitor of dihydroorotate dehydrogenase. A solution of BAY2402234 will be available to initiate the trial and there are plans to transition to a tablet form of BAY2402234 once it becomes available. Both liquid and tablet formulations of BAY2402234 will be continually administered once daily by mouth in 28 day cycles. | Drug | Dose Escalation, Dose Expansion: AML, Dose Expansion: MDS |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Up to 42 days after the first dose
The MTD was defined as the maximum dose administered during Cycle 1 at which the estimated dose-limiting toxicity (DLT) probability is closest to 30%.
Number of subjects with DLTs
Time frame: Up to 42 days after the first dose
A dose-limiting toxicity (DLT) was defined as any of the events that are clearly unrelated to underlying disease and occurring at any particular dose level during the first 28 days (i.e. Cycle 1) of treatment for non-hematological DLTs, or 42 days after the start of treatment, in the absence of active disease (i.e. < 5% blasts in bone marrow and absence of leukemic blasts in peripheral blood) for hematological DLTs. The National Cancer Institute Common Terminology Criteria for Adverse Events Version (CTCAE) v4.03 will be used to assess toxicities.
AUC(0-24) (area under the concentration versus time curve from time zero to 24 hours) after single dose on Cycle 1 Day 1 (C1D1)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after dose administration at C1D1
Cmax (maximum observed drug concentration in plasma after single dose administration) on C1D1
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours (QD cohorts=until 24 hours; BID cohort=until 12 hours) after dose administration at C1D1
AUC(0-24)md (AUC(0-24) after multiple dose) on Cycle 1 Day 15 (C1D15)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after dose administration at C1D15
Cmax,md (Cmax after multiple dose) on C1D15
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours (QD cohorts=until 24 hours; BID cohort=until 12 hours) after dose administration at C1D1
Number of subjects with Treatment Emergent Adverse Events (TEAEs)
Time frame: From first application of study intervention up to 30 days after end of treatment
An AE was any untoward medical occurrence (i.e. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study.
2 secondary outcomes
Number of acute myeloid leukemia (AML) patients with complete remission (CR) and complete response with partial recovery of peripheral blood counts (CRh)
Time frame: Up to 6 months on average
Number of myelodysplastic syndrome (MDS) patients with hematologic improvement (erythroid response, platelet response, and neutrophil response)
Time frame: Every month until disease progression or patient was withdrawn from study, up to 6 months on average
Results and safety
The study was stopped early (reason given: Lack of sufficient clinical benefit). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BAY2402234 in people with Leukemia, run by Bayer at 5 sites in 2 countries.
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 6 inclusion and 7 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: stopped early, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, France. 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 was stopped early (reason given: Lack of sufficient clinical benefit). Results are not available in the source record.
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?
Maximum tolerated dose (MTD) (time frame: Up to 42 days after the first dose). The study lists 7 primary outcomes in all. 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 11 Jan 2022.