Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia

NCT ID: NCT02345382

Last Updated: 2018-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-19
• Study Completion Date: 2017-07-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

20 mg BAY1143572

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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.

40 mg BAY1143572

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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.

80 mg BAY1143572

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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.

160 mg BAY1143572

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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.

200 mg BAY1143572

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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.

240 mg BAY1143572

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

Group Type: EXPERIMENTAL

Atuveciclib, BAY1143572

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Columbia University Medical Center

New York, New York, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Universitätsklinikum der Johann Wolfgang Goethe Universität

Frankfurt am Main, Hesse, Germany

Medizinische Fakultät Carl Gustav Carus

Dresden, Saxony, Germany

Countries

United States; Germany

Other Identifiers

2014-000410-57

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16520

Identifier Type: -

Identifier Source: org_study_id