This is a multicentric phase 2 study for previously untreated high-risk CLL patients.~A. The study treatment will consist of 6 courses of the Venetoclax + Obinutuzumab combination.~B. Patients with stable disease or a response (CR/PR) with undetectable MRD (uMRD) in the PB and BM at cycle 9 will continue treatment with Venetoclax single agent until cycle 13 and then stop treatment.~C. Patients with stable disease or a response (CR/PR) with evidence of residual disease in the PB and/or BM at cycle 9 will continue treatment with Venetoclax and Zanubrutinib (VenZan) combination until cycle 21.~c1. Patients with uMRD in the PB and BM at cycle 21 will stop treatment. c2. Patients with residual disease in the PB and/or BM at cycle 21 will discontinue Venetoclax and continue Zanubrutinib until disease progression.~In all patients with uMRD, MRD will be monitored during the follow-up. Patients with a response with uMRD in the PB and BM who subsequently develop an MRD positivity will not be treated. A new treatment will start at the time of clinical disease progression according to the iwCLL criteria.
Multicentric phase 2 study for previously untreated high-risk CLL patients. Patients will receive 6 courses of the Venetoclax + Obinutuzumab combination.~Patients with stable disease or a response (CR/PR) with uMRD in the PB and BM at cycle 9 will continue treatment with Venetoclax single agent until cycle 13 and then stop treatment.~Patients with stable disease or a response (CR/PR) with evidence of residual disease in the PB and/or BM at cycle 9 will continue treatment with Venetoclax and Zanubrutinib combination until cycle 21.~then, Patients with uMRD in the PB and BM at cycle 21 will stop treatment whereas patients with residual disease in the PB and/or BM at cycle 21 will discontinue Venetoclax and continue Zanubrutinib until disease progression.