Study Completed

Leukemia

Bayer Identifier:

16520

ClinicalTrials.gov Identifier:

NCT02345382

EudraCT Number:

2014-000410-57

EU CT Number:

Not Available

Phase I dose escalation of BAY1143572 in subjects with acute leukemia

Trial purpose

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

Key Participants Requirements

Sex

Both

Age

18 - N/A

Inclusion Criteria
- 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 -- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) -- International normalized ratio (INR) -- 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.
Exclusion Criteria
- 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
- 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

Trial summary

Enrollment Goal

Trial Dates

February 2015 - July 2017

Phase

Phase 1

Could I Receive a placebo

Products

Atuveciclib (BAY1143572)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Universitätsklinikum der Johann Wolfgang Goethe Universität	Frankfurt, 60596, Germany
Completed	Dana-Farber Cancer Institute	Boston, 02215, United States
Completed	Medizinische Fakultät Carl Gustav Carus	Dresden, 01307, Germany
Completed	Columbia University Medical Center	New York, 10032, United States
Withdrawn	Universitätsklinikum Münster (UKM)	Münster, 48149, Germany
Completed	Medical University of South Carolina	Charleston, 29425, United States
Completed	Vanderbilt University Medical Center	Nashville, 37232, United States
Completed	Hackensack University Medical Center	Hackensack, 07601, United States

Primary Outcome

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.
Time Frame:
After the first 28 days of treatment (cycle 1)
Safety Issue:
Yes
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.
Time Frame:
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.
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 (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.
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 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.
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 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.
Time Frame:
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.
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 Multiple Dose Administration (tmax,md)
Time to reach maximum drug concentration of BAY1143572 in plasma after multiple dose administration was measured.
Time Frame:
Pre-dose up to 24 hours post-dose on Cycle 1 Day 15

Secondary Outcome

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.
Time Frame:
From start of treatment of the first subject until 28 days
Safety Issue:
Yes
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.
Time Frame:
From start of study drug administration up to 30 days after the last dose of study drug administration (approximately 2.5 years)
Safety Issue:
No
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.
Time Frame:
Pre-dose up to 24 hours post-dose on C1D1

Trial design

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

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

Non-randomized

Blinding

Open Label

Assignment

Parallel Assignment

Trial Arms

Additional Information

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