Background: The German CLL study group (GCLLSG) performed three similar phase-II-trials combining a CD20-antibody, ofatumumab (O) or obinutuzumab (G, for GA-101), with ibrutinib (I) or venetoclax (A) in an all-comer population of treatment-naïve or relapsed/refractory CLL patients (pts). Methods: In all 3 trials, pts with high tumor burden received optional bendamustine debulking (BD). Subsequent induction therapy consisted of 6 cycles of I plus O (BIO trial), or I plus G (BIG) or A plus G (BAG). Induction therapy was followed by a maintenance phase using the same drugs until achieving a minimal residual disease (MRD) negative complete remission or up to 24 months. The primary endpoint was the overall response rate (ORR) at the end of induction; secondary endpoints were MRD and safety. Results: 66 pts each were enrolled in the 3 trials. Pts with < 2 induction cycles were excluded from the analysis as per protocol, resulting in 65, 61 and 63 evaluable pts in BIO, BIG and BAG, respectively. The primary endpoint was met in all trials. BD achieved an ORR of 61 % across all trials. During combination therapy one fatal adverse event occurred in each trial; during induction 46 SAEs occurred in BIO, 29 in BIG and 59 in BAG. Patients? characteristics and major results are shown in the Table. Conclusions: The sequential combination concept shows very good efficacy and tolerability. BD reduced the number of IRR. Combination therapies with G seemed more efficient when compared to O. Additionally, combining A plus G seemed to evoke deeper responses than I plus G. Clinical trial information: NCT02689141, NCT02401503 and NCT02345863