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Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia

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ClinicalTrials.gov Identifier: NCT02345382
Recruitment Status : Completed
First Posted : January 26, 2015
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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

Condition or disease Intervention/treatment Phase
Leukemia Drug: Atuveciclib, BAY1143572 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 19, 2015
Actual Primary Completion Date : September 14, 2016
Actual Study Completion Date : July 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: 20 mg BAY1143572
Subjects received 20 milligram (mg) BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.

Experimental: 40 mg BAY1143572
Subjects received 40 mg BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.

Experimental: 80 mg BAY1143572
Subjects received BAY1143572 80 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.

Experimental: 120 mg BAY1143572
Subjects received BAY1143572 120 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.

Experimental: 160 mg BAY1143572
Subjects received BAY1143572 160 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.

Experimental: 200 mg BAY1143572
Subjects received BAY1143572 200 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.

Experimental: 240 mg BAY1143572
Subjects received BAY1143572 240 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.
Drug: Atuveciclib, BAY1143572
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.


Secondary Outcome Measures :
  1. Number of Subjects With Leukemia Response [ Time Frame: From start of treatment of the first subject until 28 days ]
    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.

  2. 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) ]
    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.

  3. 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 ]
    Area under the concentration versus time curve from zero to infinity of BAY1143572 after single dose administration in plasma was measured.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02345382


Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Germany
Universitätsklinikum der Johann Wolfgang Goethe Universität
Frankfurt, Hessen, Germany, 60596
Medizinische Fakultät Carl Gustav Carus
Dresden, Sachsen, Germany, 01307
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02345382     History of Changes
Other Study ID Numbers: 16520
2014-000410-57 ( EudraCT Number )
First Posted: January 26, 2015    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Advanced acute leukemia

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms