Phase I Dose Escalation of BAY1143572 in Subjects With Acute Leukemia

Bayer

Status and phase: Completed; Phase 1

Conditions: Leukemia

Treatments: Drug: Atuveciclib, BAY1143572

Study type: Interventional

Funder types: Industry

Identifiers

NCT02345382

16520

2014-000410-57 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 7 patient groups

20 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572

40 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572

80 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572

120 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572

160 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572

200 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572

240 mg BAY1143572

Experimental group

Description:

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

Treatment:

Drug: Atuveciclib, BAY1143572