Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia

NCT02345382 | Completed Phase 1 FDA Drug

• 2 other identifiers: 165202014-000410-57
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 7

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

Conditions

Leukemia

Keywords

Advanced acute leukemia

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Pre-dose up to 24 hours post-dose on Cycle 1 Day 15

Secondary Outcomes (3)

• Number of Subjects With Leukemia Response

  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)

  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

  Pre-dose up to 24 hours post-dose on C1D1

Study Arms (7)

20 mg BAY1143572

EXPERIMENTAL

Subjects received 20 milligram (mg) BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

40 mg BAY1143572

EXPERIMENTAL

Subjects received 40 mg BAY1143572 tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

80 mg BAY1143572

EXPERIMENTAL

Subjects received BAY1143572 80 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

120 mg BAY1143572

EXPERIMENTAL

Subjects received BAY1143572 120 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

160 mg BAY1143572

EXPERIMENTAL

Subjects received BAY1143572 160 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

200 mg BAY1143572

EXPERIMENTAL

Subjects received BAY1143572 200 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

240 mg BAY1143572

EXPERIMENTAL

Subjects received BAY1143572 240 mg tablet orally once daily from Cycle 1 Day 1 of each cycle.

Drug: Atuveciclib, BAY1143572

Interventions

Atuveciclib, BAY1143572 DRUG

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.

120 mg BAY1143572; 160 mg BAY1143572; 20 mg BAY1143572; 200 mg BAY1143572; 240 mg BAY1143572; 40 mg BAY1143572; 80 mg BAY1143572

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (7)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Universitätsklinikum der Johann Wolfgang Goethe Universität

Frankfurt am Main, Hesse, 60596, Germany

Location

Medizinische Fakultät Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

MeSH Terms

Conditions

Leukemia

Interventions

atuveciclib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: January 26, 2015
• Study Start: February 19, 2015
• Primary Completion: September 14, 2016
• Study Completion: July 30, 2017
• Last Updated: June 25, 2018

Record last verified: 2018-06

Locations

US (5); DE (2)