Mazyar Shadman, MD, MPH, on Chronic Lymphocytic Leukemia: Recruiting for the CELESTIAL-TNCLL Study

This year at the ASCO meeting, I had the opportunity of presenting a trial in progress. This is CELESTRIAL-CLLTN trial, which is a global head-to-head Phase III trial comparing the investigational combination using zanubrutinib, a second generation BTK inhibitor, in combination with sonrotoclax, which is a novel BCL2 inhibitor, and we are comparing that to a standard arm of venetoclax plus obinutuzumab for treatment of first line CLL patients who require treatment. As a background, we currently have two options for first line treatment of CLL. We either go with continuous BTK inhibitor therapy until progression or intolerance, or we use a time-limited approach using venetoclax in combination with obinutuzumab. If the study is positive, we'll introduce another time-limited option, which is all oral and chemoimmunotherapy free. Zanubrutinib is already approved for CLL in all lines of therapy, and in clinical trial has been shown to be superior to ibrutinib both from the efficacy and safety standpoint. Sonrotoclax is a novel BCL2 inhibitor, has shown very promising activity both from the safety and efficacy standpoints. In fact, in a study that was presented at ASH in 2023, we saw an extremely effective combination and also very well-tolerated treatment option for CLL patients. What this study is trying to do is comparing sonrotoclax and zanubrutinib to venetoclax and obinutuzumab. This is a global study with more than 640 patients planned to be enrolled, and patients will be randomized to receive one of the two options. The primary endpoint is progression-free survival, and we are going for superiority of the investigational arm over the standard of care arm. This study is currently ongoing, and we encourage our colleagues to contact the participating sites and PIs if they have any patients who requires treatment for first line CLL.