Clinical trial NCT02345382: Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: Advanced acute leukemia
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-01-26
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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 \</=1.5 times the upper limit of normal (ULN)
  * 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.

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 \</=4 months before first dose of study drug (Subjects must have completed immunosuppressive therapy before enrollment.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of BAY1143572 in Advanced Acute Leukemia Subjects
timeFrame: After the first 28 days of treatment (cycle 1)
measure: Maximum Total Observed Drug Concentration (Cmax) of BAY1143572 after Single Dose Administration in Plasma
timeFrame: Pre-dose up to 24 hours post-dose on Cycle1 Day 1
measure: Maximum Total Observed Drug Concentration of BAY1143572 after Multiple Dose Administration in Plasma (Cmax,md)
timeFrame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
measure: Area Under the Concentration Versus Time Curve from Zero to 24 hours (AUC[0-24h]) of BAY1143572 in Plasma After Single Dose Administration
timeFrame: Pre-dose up to 24 hours post-dose on Cycle1 Day 1
measure: Area Under the Concentration Versus Time Curve from Zero to 24 hours of BAY1143572 in Plasma after Multiple Dose Administration (AUC[O-24h]md)
timeFrame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
measure: 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
timeFrame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 1
measure: Time to Reach Maximum Drug Concentration (tmax) of BAY1143572 in Plasma after Single Dose Administration
timeFrame: pre-dose up to 24 hours post-dose on Cycle 1 Day 1
measure: Time to Reach Maximum Drug Concentration of BAY1143572 in Plasma after Multiple Dose Administration (tmax,md)
timeFrame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15
Secondary outcomes:
measure: Number of Subjects With Leukemia Response
timeFrame: From start of treatment of the first subject until 28 days
measure: Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study drug administration up to 30 days after the last dose of study drug administration (approximately 2.5 years)
measure: Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC) of BAY1143572 after Single Dose Administration in Plasma
timeFrame: Pre-dose up to 24 hours post-dose on C1D1
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Frankfurt
country: Germany
facility: Universitätsklinikum der Johann Wolfgang Goethe Universität
state: Hessen
city: Dresden
country: Germany
facility: Medizinische Fakultät Carl Gustav Carus
state: Sachsen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: