AVO-CLL: a phase III multicenter, randomized, open-label, clinical trial comparing efficacy and safety of acalabrutinib in combination with obinutuzumab versus venetoclax in combination with obinutuzumab in the first-line treatment of newly diagnosed patients with chronic lymphocytic leukemia

Lab values

• Any previous systemic treatment for CLL 2. Diagnosis of CNS lymphoma or leukemia 3. Diagnosed prolymphocytic leukemia or previous or suspected Richter's syndrome; 4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purple 5. Major surgery within 4 weeks before the first dose of IMP 6. Previous malignancy, except appropriately treated melanoma arising from malignant lentigo, non-melanoma skin cancer, cervical cancer “in situ”, or other treated malignancy without evidence of active disease >3 years prior to screening and at low risk of recurrence 7. Serious cardiovascular disease, e.g., uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months before study entry, or any New York Heart Association Functional Classification class 3 or 4 heart disease or QTc >480 msec before entering the study 8. Previous stroke or intracranial hemorrhage within 6 months before randomization; 9. Current or planned anticoagulant treatment with warfarin or vitamin K antagonists within 7 days of the first dose of the study drug 10. Current or planned treatment with proton pump inhibitors 11. Current or planned treatment with a strong CYP3A inhibitor/inducer 12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before the screening visit 13. history of HIV infection 14. History of bleeding disorders 15. The presence of contraindications to use of IMP according to Summary of Product Characteristics 16. Lack of full legal capacity 17. Lack of possibility to understand the purpose

• Written informed consent to participate in a clinical trial 2. Age of patients over 18 years (women and men) 3. Diagnosis of chronic lymphocytic leukemia untreated before the screening visit 4. Presence of the following parameters during the screening period: - presence of monoclonal lymphocytes with co-expression of B cell markers (CD19, CD20 and CD23) and CD5 - prolymphocyte count <55% of peripheral blood lymphocyte count - absolute number of peripheral blood lymphocytes > 5000 /ul 5. Presence of indications to start treatment according to the International Workshop on Chronic Lymphocytic Leukemia (the National Cancer Institute-Working Group (IWCLL) 2018. 6. Laboratory test results: - absolute ANC number ≥0.75 x 109 /l or ≥0.50x109 /l in patients with documented bone marrow involvement; - platelet count ≥50x10 /l or ≥30x109 /l in patients with documented bone marrow involvement; - total bilirubin ≤1.5xULN; - AST, ALT, GGT in serum ≤3.0xULN; - estimated creatinine clearance (eGFR) ≥30 ml/min; - negative test result for HBsAg and HBcAg 7. ECOG performance assessment score ≤2. 8. Use of effective contraception by women of childbearing potential during treatment and at least 2 days after the last dose of acalabrutinib, 30 days after the last dose of venetoclax and 18 months after the last dose of obinutuzumab 9. Use of an effective form of contraception by men during the study and 90 days after taking the last dose of the IMP 10. Men must refrain from donating sperm during the study and for 90 days after taking the last dose of the study drug