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

INTERVENTION: Product Name: Gazyvaro 1,000 mg concentrate for solution for infusion.,Product Code: PRD1753415,Pharmaceutical Form: SOLUTION FOR INFUSION,Other descriptive name: ,Strength: Obinutuzumab 1000mg / 40mL,Product Name: Venclyxto 10 mg film‐coated tablets,Product Code: PRD6353822,Pharmaceutical Form: FILM‐COATED TABLET,Other descriptive name: ,Strength: Venetocla X10mg,Product Name: Calquence 100 mg hard capsules,Product Code: PRD8485702,Pharmaceutical Form: CAPSULE, HARD,Other descriptive name: ,Strength: Acalabrutinib 100mg,Product Name: Venclyxto 100 mg film‐coated tablets,Product Code: PRD6353838,Pharmaceutical Form: FILM‐COATED TABLET,Other descriptive name: ,Strength: Venetocla X100mg,Product Name: Venclyxto 50 mg film‐coated tablets,Product Code: PRD6353830,Pharmaceutical Form: FILM‐COATED TABLET,Other descriptive name: ,Strength: Venetocla X50mg CONDITION: Chronic lymphocytic leukemia ; MedDRA version: 21.0Level: LLTClassification code: 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 MedDRA version: 21.0Level: LLTClassification code: 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 Therapeutic area: Diseases [C] ‐ Neoplasms [C04] PRIMARY OUTCOME: Main Objective:Main objective of the study: to evaluate the therapeutic efficacy, safety and tolerability of acalabrutinib in combination with obinutuzumab versus venetoclax in combination with obinutuzumab in the treatment of patients with chronic lymphocytic leukemia. Primary end point(s):Primary endpoint Progression‐free survival (PFS), defined as the time from randomization to progression or death, a clinically important endpoint. Secondary Objective:Additional aim of the study: to assess the quality of life of study participants using the EORTC QLQ‐c30, EQ‐5D, FACIT‐Fatigue questionnaires and to compare the results of the group of participants treated with acalabrutinib in combination with obinutuzumab (group A) with the group of participants treated with venetoclax combined with obinutuzumab (group B). ). ? SECONDARY OUTCOME: Secondary end point(s):Secondary endpoints Response to treatment (including MRD), time to next line of treatment. The amount of change in quality of life. Treatment safety based on the assessment of adverse events. Overall survival is defined as the time from randomization to death from any cause. INCLUSION CRITERIA: 1. 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 X109 /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 creatinin