An Open-label, Multicenter Phase I Study to Characterize the Safety, Tolerability, Preliminary Anti-tumor Activity, Pharmacokinetics and Maximum Tolerated Dose of BAY1251152 in Patients With Advanced Hematological Malignancies
Overview
- Phase
- Phase 1
- Intervention
- BAY1251152
- Conditions
- Hematologic Neoplasms
- Sponsor
- Bayer
- Enrollment
- 21
- Primary Endpoint
- Maximum tolerated dose(MTD)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to identify the most appropriate dose that can be safely administered and that can have an effect on blood cancer cells. Once that safe dose is identified, additional patients will be asked to join the study to further evaluate the safety and effectiveness of the study drug. The study will also investigate the pharmacokinetics (study of what the body does to the drug), as well as pharmacodynamics (study of what the drug does to the body), which may provide information about the effects of BAY 1251152. The study will also measure some biological markers (markers of biological activity in your body) that can be used to predict the response and safety of the proposed treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged ≥18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and Life expectancy of at least 12 weeks
- •Patients are able and willing to provide bone marrow biopsies/aspirates as requested by the protocol
- •Patients with confirmed advanced hematological malignancies
- •Negative serum pregnancy test
- •Women and men of reproductive potential must agree to use highly effective contraception when sexually active.
- •Ability to understand and the willingness to sign a written informed consent.
- •Patients must have adequate coagulation (international normalized ratio (INR) or prothrombin time (PT), partial thromboplastin time (PTT) ≤1.5 times ULN)
- •Adequate liver function (total bilirubin ≤ 1.5 times the ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN
Exclusion Criteria
- •Presence of active/uncontrolled central nervous system involvement
- •History of clinically significant cardiac disease; uncontrolled hypertension
- •Left ventricular ejection fraction (LVEF) \< 45%
- •Allogeneic stem cell transplant within 100 days before first dose of study drug
- •Known history of human immunodeficiency virus (HIV) infection
- •Chronic or active hepatitis B or C, requiring antiviral therapy
- •Evidence of history of bleeding disorder, dialysis, or coexisting cancer that is distinct in primary site or histology from the cancer evaluated in this study
- •Serious, uncontrolled infection
- •Unresolved chronic toxicity \> grade 1 from prior therapy
- •Use of strong CYP3A4 inhibitors or strong inducers within 7 days prior to the start of study treatment and for the duration of the study
Arms & Interventions
Arm 1
Biomarker-enriched advanced hematological neoplasms
Intervention: BAY1251152
Arm 2
Other selected advanced hematological neoplasms
Intervention: BAY1251152
Outcomes
Primary Outcomes
Maximum tolerated dose(MTD)
Time Frame: 21 days
To determine the MTD of BAY1251152 in subjects with advanced hematological neoplasms
Pharmacokinetics (PK) is determined by maximum concentration (Cmax)
Time Frame: 21 days
Number of adverse events (AE)
Time Frame: Up to 30 months
For assessment of the safety (ECG, vital signs, clinical significant abnormal laboratory results... etc.)and tolerability of BAY 1251152 in subjects with advanced hematological neoplasms
Recommended Phase 2 dose (RP2D)
Time Frame: Up to 30 months
To determine the RP2D of BAY1251152 based on safety, tolerability, pharmacokinetic, and pharmacodynamic data in subjects with advanced hematological neoplasms
Pharmacokinetics (PK) is determined by Area Under concentration versus time Curve (AUC)
Time Frame: 21 days
Secondary Outcomes
- Response assessment of BAY 1251152 in hematological malignancies based on the internationally accepted criteria for the specific hematological malignancy which patient is suffering from(Up to 30 months)