M24-287 M24-287 A two-part, prospective, open-label, phase IIb/III study to evaluate the risk of tumour lysis syndrome (TLS) and optimisation of the initiation of venetoclax in combination with obinutuzumab or acalabrutinib with different initiation and ramp-up periods in previously untreated CLL patients

This is an open-label, multi-arm, international, multicenter, two-part, Phase IIb/III study. Part 1 of the study will evaluate TLS-related safety events of venetoclax in different combinations and dosing rampup periods in previously untreated subjects with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy. In Part 1, approximately 120 subjects from approximately 80 centers globally will be randomized in a 1:1:1:1 ratio to one of the following four arms: • Arm A: Venetoclax + obinutuzumab with a 5-week venetoclax ramp-up • Arm B: Venetoclax + acalabrutinib with a 5-week venetoclax ramp-up • Arm C: Venetoclax + acalabrutinib with a 6-week venetoclax ramp-up • Arm D: Venetoclax + acalabrutinib with a 7-week venetoclax ramp-up The study regimens will be administered over a fixed duration, starting from the initiation of debulking agents. Each study Arm (Arm A, Arm B, Arm C, and Arm D) will have a designated duration of 12 cycles, 14 cycles, 15 cycles, and 15 cycles, respectively. The conclusion of the specified number of cycles for each Arm will signify the completion of the respective fixed duration treatment.