LeukemiaPhase 1NCT02345382
Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia
A Phase 1 study testing Atuveciclib, BAY1143572 in people with Leukemia, run by Bayer at 7 sites in 2 countries.
Trial summary
To determine the safety, tolerability, pharmacokinetics, maximum tolerated dose, and recommended Phase II dose of BAY1143572 in a once-daily or an intermittent dosing schedule in subjects with advanced acute leukemia Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- Atuveciclib, BAY1143572
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 19 Feb 2015to 30 Jul 2017
- 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
- Male or female subjects aged >/=18 years
- Subjects with a histologically or cytologically confirmed acute leukemia who are refractory to or have exhausted all available therapies
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Life expectancy of at least 12 weeks
- Adequate liver and renal functions as assessed by the following laboratory requirements to be conducted within 14 days before the first dose of study drug:
- Total bilirubin </=1.5 times the upper limit of normal (ULN)
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- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </=2.5 times ULN (</=5 times ULN for subjects with liver involvement of their cancer)
- International normalized ratio (INR) </=1.5 times ULN
- Estimated glomerular filtration rate (eGFR) >/=50 mL/min per 1.73 m2 according to the Modification of Diet in Renal Disease Study Group (MDRD) formula
- Negative serum or urine pregnancy test must be obtained within 7 days before the first dose of study drug in women of childbearing potential. Negative results must be available before study drug administration
- Women and men of reproductive potential must agree to use highly effective contraception when sexually active. This applies for the period between signing of the informed consent and 30 days after the last administration of study drug. Highly effective contraception includes a hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices, bilateral tubal ligation, hysterectomy, or vasectomy of the partner. In addition, the use of condoms for subjects or their partners is required.
Who cannot join
- Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study
- History of cardiac disease including congestive heart failure New York Heart Association (NYHA) Class >/=III, unstable angina (anginal symptoms at rest) or new-onset angina (within the last 6 months) or myocardial infarction within the past 6 months or cardiac arrhythmias requiring anti-arrhythmic therapy except for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (e.g. major regional wall motion abnormalities on baseline echocardiography or a left ventricular ejection fraction (LVEF) <45%)
- Previous pulmonary embolism within 12 months before study entry
- Uncontrolled hypertension defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg, despite optimal medical management and stable antihypertensive treatment for more than 7 days before the first dose of study drug
- Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
- Known history of human immunodeficiency virus (HIV) infection
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- Chronic or active hepatitis B or C, requiring antiviral therapy
- Serious, uncontrolled infection requiring systemic antibiotic, antifungal or antiviral therapy
- Uncontrolled meningeal leukemia
- Prior allogeneic hematopoietic stem cell transplant within </=4 months before first dose of study drug (Subjects must have completed immunosuppressive therapy before enrollment.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Medical University of South Carolina
Charleston, South Carolina, 29425
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University Medical Center
New York, New York, 10032
Germany2 sites
Medizinische Fakultät Carl Gustav Carus
Dresden, Saxony, 01307
Universitätsklinikum der Johann Wolfgang Goethe Universität
Frankfurt am Main, Hesse, 60596
About this study
Official title: An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY1143572 Given in a Once-daily or an Intermittent Dosing Schedule in Subjects With Advanced Acute Leukemia
To determine the safety, tolerability, pharmacokinetics, maximum tolerated dose, and recommended Phase II dose of BAY1143572 in a once-daily or an intermittent dosing schedule in subjects with advanced acute leukemia
- Conditions
- Leukemia
- Being tested
- Atuveciclib, BAY1143572
- Keywords
- Advanced acute leukemia
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atuveciclib, BAY1143572Drug
The starting dose was 20 mg BAY 1143572 once daily from Cycle 1 Day 1. Each cycle was defined as a period of 28 days. Dosing cycles continued until evidence of progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator.
| Study group | Role | What they receive |
|---|---|---|
| 20 mg BAY1143572 | Experimental | Subjects received 20 milligram (mg) BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
| 40 mg BAY1143572 | Experimental | Subjects received 40 mg BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
| 80 mg BAY1143572 | Experimental | Subjects received BAY1143572 80 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
| 120 mg BAY1143572 | Experimental | Subjects received BAY1143572 120 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
| 160 mg BAY1143572 | Experimental | Subjects received BAY1143572 160 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
| 200 mg BAY1143572 | Experimental | Subjects received BAY1143572 200 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
| 240 mg BAY1143572 | Experimental | Subjects received BAY1143572 240 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. Receives: Drug: Atuveciclib, BAY1143572 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of BAY1143572 in Advanced Acute Leukemia Subjects
The MTD was defined as the highest dose that could be given such that not more than 20% of subjects experience a dose limiting toxicity (DLT) during Cycle 1. The study was terminated prior to the determination of MTD and hence no data was presented.
Measured: After the first 28 days of treatment (cycle 1)
Maximum Total Observed Drug Concentration (Cmax) of BAY1143572 after Single Dose Administration in Plasma
Maximum total observed drug concentration of BAY1143572 after single dose administration in plasma was measured.
Measured: Pre-dose up to 24 hours post-dose on Cycle1 Day 1
Maximum Total Observed Drug Concentration of BAY1143572 after Multiple Dose Administration in Plasma (Cmax,md)
Maximum total observed drug concentration of BAY1143572 after multiple dose administration in plasma was measured.
Measured: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Area Under the Concentration Versus Time Curve from Zero to 24 hours (AUC[0-24h]) of BAY1143572 in Plasma After Single Dose Administration
Area under the concentration versus time curve from zero to 24 hours of BAY1143572 in plasma after single dose administration was measured.
Measured: Pre-dose up to 24 hours post-dose on Cycle1 Day 1
Area Under the Concentration Versus Time Curve from Zero to 24 hours of BAY1143572 in Plasma after Multiple Dose Administration (AUC[O-24h]md)
Area under the concentration versus time curve from zero to 24 hours of BAY1143572 in plasma after multiple dose administration was measured.
Measured: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Area Under the Concentration Versus Time Curve from Zero to Last Data Point Greater than Lower Limit of Quantitation (LLOQ) of BAY1143572 in Plasma (AUC[0-tlast]) after Single Dose Administration
Area under the concentration versus time curve from zero to last data point greater than lower limit of quantitation of BAY1143572 in plasma after single dose administration was measured.
Measured: Pre-dose up to 24 hours post-dose on Cycle 1 Day 1
Time to Reach Maximum Drug Concentration (tmax) of BAY1143572 in Plasma after Single Dose Administration
Time to reach maximum drug concentration of BAY1143572 in plasma after single dose administration was measured.
Measured: pre-dose up to 24 hours post-dose on Cycle 1 Day 1
Time to Reach Maximum Drug Concentration of BAY1143572 in Plasma after Multiple Dose Administration (tmax,md)
Time to reach maximum drug concentration of BAY1143572 in plasma after multiple dose administration was measured.
Measured: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Secondary outcomes (3)
Number of Subjects With Leukemia Response
Bone marrow aspirates / biopsies / peripheral whole blood were taken and assessed for leukemia response evaluation. Assessment of response was made based on the revised recommendations of the International Working Group (Cheson 2003 criteria). Criteria proposed by Cheson 2003 for leukemia: complete remission (CR), morphological CR with incomplete blood count recovery (CRi), partial remission (PR), no response / treatment failure, relapse from CR, CRi, or PR.
Measured: From start of treatment of the first subject until 28 days
Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. AEs that started or worsened after first administration of study medication up to 30 days after end of treatment with study medication were considered to be treatment emergent (TE). A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly and another medical important serious event as judged by investigator. SAEs that started or worsened after study drug treatment were recorded as TESAEs.
Measured: From start of study drug administration up to 30 days after the last dose of study drug administration (approximately 2.5 years)
Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC) of BAY1143572 after Single Dose Administration in Plasma
Area under the concentration versus time curve from zero to infinity of BAY1143572 after single dose administration in plasma was measured.
Measured: Pre-dose up to 24 hours post-dose on C1D1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2015 (estimated)
- Study start19 Feb 2015
- Primary completion14 Sep 2016
- Study completion30 Jul 2017
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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02345382
- Sponsor's protocol ID
- 16520
- Other IDs
- 2014-000410-57, 2014
- Status last verified
- Jun 2018
- First submitted
- 20 Jan 2015
- Last updated
- 25 Jun 2018
- 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 25 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY1143572 Given in a Once-daily or an Intermittent Dosing Schedule in Subjects With Advanced Acute Leukemia
- ClinicalTrials.gov ID
- NCT02345382
- Acronym / sponsor ID
- 16520
- Conditions
- Leukemia
- Keywords
- Advanced acute leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 19 Feb 2015 (actual)
- Primary completion
- 14 Sep 2016 (actual)
- Study completion
- 30 Jul 2017 (actual)
- First posted
- 26 Jan 2015 (estimated)
- 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.
To determine the safety, tolerability, pharmacokinetics, maximum tolerated dose, and recommended Phase II dose of BAY1143572 in a once-daily or an intermittent dosing schedule in subjects with advanced acute leukemia
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 20 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received 20 milligram (mg) BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle. |
| 40 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received 40 mg BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle. |
| 80 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received BAY1143572 80 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. |
| 120 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received BAY1143572 120 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. |
| 160 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received BAY1143572 160 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. |
| 200 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received BAY1143572 200 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. |
| 240 mg BAY1143572 | Experimental | Drug: Atuveciclib, BAY1143572Subjects received BAY1143572 240 mg tablet orally once daily from Cycle 1 Day 1 of each cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female subjects aged >/=18 years
- Subjects with a histologically or cytologically confirmed acute leukemia who are refractory to or have exhausted all available therapies
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Life expectancy of at least 12 weeks
- Adequate liver and renal functions as assessed by the following laboratory requirements to be conducted within 14 days before the first dose of study drug:
Key exclusion criteria (10 listed)
- Known hypersensitivity to the study drug or excipients of the preparation or any agent given in association with this study
- History of cardiac disease including congestive heart failure New York Heart Association (NYHA) Class >/=III, unstable angina (anginal symptoms at rest) or new-onset angina (within the last 6 months) or myocardial infarction within the past 6 months or cardiac arrhythmias requiring anti-arrhythmic therapy except for beta-blockers and digoxin; evidence for uncontrolled coronary artery disease (e.g. major regional wall motion abnormalities on baseline echocardiography or a left ventricular ejection fraction (LVEF) <45%)
- Previous pulmonary embolism within 12 months before study entry
- Uncontrolled hypertension defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg, despite optimal medical management and stable antihypertensive treatment for more than 7 days before the first dose of study drug
- Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C
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 |
|---|---|---|
| Atuveciclib, BAY1143572The starting dose was 20 mg BAY 1143572 once daily from Cycle 1 Day 1. Each cycle was defined as a period of 28 days. Dosing cycles continued until evidence of progression, unacceptable toxicity, consent withdrawal, or withdrawal from the study at the discretion of the investigator. | Drug | 120 mg BAY1143572, 160 mg BAY1143572, 20 mg BAY1143572, 200 mg BAY1143572, 240 mg BAY1143572, 40 mg BAY1143572, 80 mg BAY1143572 |
Primary outcome
Maximum Tolerated Dose (MTD) of BAY1143572 in Advanced Acute Leukemia Subjects
Time frame: After the first 28 days of treatment (cycle 1)
The MTD was defined as the highest dose that could be given such that not more than 20% of subjects experience a dose limiting toxicity (DLT) during Cycle 1. The study was terminated prior to the determination of MTD and hence no data was presented.
Maximum Total Observed Drug Concentration (Cmax) of BAY1143572 after Single Dose Administration in Plasma
Time frame: Pre-dose up to 24 hours post-dose on Cycle1 Day 1
Maximum total observed drug concentration of BAY1143572 after single dose administration in plasma was measured.
Maximum Total Observed Drug Concentration of BAY1143572 after Multiple Dose Administration in Plasma (Cmax,md)
Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Maximum total observed drug concentration of BAY1143572 after multiple dose administration in plasma was measured.
Area Under the Concentration Versus Time Curve from Zero to 24 hours (AUC[0-24h]) of BAY1143572 in Plasma After Single Dose Administration
Time frame: Pre-dose up to 24 hours post-dose on Cycle1 Day 1
Area under the concentration versus time curve from zero to 24 hours of BAY1143572 in plasma after single dose administration was measured.
Area Under the Concentration Versus Time Curve from Zero to 24 hours of BAY1143572 in Plasma after Multiple Dose Administration (AUC[O-24h]md)
Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Area under the concentration versus time curve from zero to 24 hours of BAY1143572 in plasma after multiple dose administration was measured.
Area Under the Concentration Versus Time Curve from Zero to Last Data Point Greater than Lower Limit of Quantitation (LLOQ) of BAY1143572 in Plasma (AUC[0-tlast]) after Single Dose Administration
Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 1
Area under the concentration versus time curve from zero to last data point greater than lower limit of quantitation of BAY1143572 in plasma after single dose administration was measured.
Time to Reach Maximum Drug Concentration (tmax) of BAY1143572 in Plasma after Single Dose Administration
Time frame: pre-dose up to 24 hours post-dose on Cycle 1 Day 1
Time to reach maximum drug concentration of BAY1143572 in plasma after single dose administration was measured.
Time to Reach Maximum Drug Concentration of BAY1143572 in Plasma after Multiple Dose Administration (tmax,md)
Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Time to reach maximum drug concentration of BAY1143572 in plasma after multiple dose administration was measured.
3 secondary outcomes
Number of Subjects With Leukemia Response
Time frame: From start of treatment of the first subject until 28 days
Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From start of study drug administration up to 30 days after the last dose of study drug administration (approximately 2.5 years)
Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC) of BAY1143572 after Single Dose Administration in Plasma
Time frame: Pre-dose up to 24 hours post-dose on C1D1
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 25 Jun 2018.
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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.
Bayer Study Director study director
Bayer
7 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 Atuveciclib, BAY1143572 in people with Leukemia, run by Bayer at 7 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 11 inclusion and 10 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 25 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Germany. 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?
Maximum Tolerated Dose (MTD) of BAY1143572 in Advanced Acute Leukemia Subjects (time frame: After the first 28 days of treatment (cycle 1)). The study lists 8 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 25 Jun 2018.