Treatment of Chronic Lymphocytic Leukemia (CLL) in Cases of Recurrent Disease Activity with Venetoclax and Obinutuzumab Following Prior Treatment with Venetoclax

Chronic lymphocytic leukemia (CLL) is characterized by the uncontrolled proliferation of B lymphocytes, a subtype of white blood cells. Treatment is usually not initiated until symptoms appear. The choice of medications depends on the patient’s overall health, comorbidities, and the characteristics of the CLL cells. Modern therapy includes drugs that specifically target structures in CLL cells, such as so-called Bcl-2 inhibitors. These include venetoclax, which is taken in tablet form. A CD20 antibody is also frequently used; it recognizes the CD20 surface marker on cancer cells and thereby kills them. Examples include rituximab and the newer antibody obinutuzumab. Both are administered as infusions. A standard first-line therapy is the time-limited combination of venetoclax and rituximab (VenR).

The goal of the ReVenG study is to test whether re-administration of venetoclax together with obinutuzumab (VenO) is effective when patients have already been treated with venetoclax and a CD20 antibody as part of their initial therapy and now have a relapse requiring treatment. Both drugs used in this study are already approved in this combination (VenO) — as first- or second-line therapy — but what is new is that this combination is to be used following prior VenR therapy. Patients are divided into two groups based on how long they remained disease-free (in remission) after their first VenR treatment. Group 1 consists of patients who experienced a relapse 12 to 24 months after VenR. Group 2 includes those whose remission lasted longer than 24 months. The disease-free interval must therefore have been at least 12 months for all patients. All patients participating in the study will receive treatment with VenO. However, the duration of venetoclax administration differs: In Group 1, patients receive 6 cycles of venetoclax plus obinutuzumab, followed by another 6 cycles of venetoclax alone (total duration of venetoclax: 12 months). In Group 2, they receive 6 cycles of venetoclax plus obinutuzumab, followed by another 18 cycles of venetoclax alone (total duration of venetoclax: 24 months). One cycle lasts 28 days. Follow-up after the end of treatment continues for approximately 15 months. The primary endpoint is the complete response rate (CR/CRi) at the end of the VenO combination phase (after 6 months).

Women and men aged 18 and older with chronic lymphocytic leukemia (CLL) who have experienced a relapse following first-line therapy with venetoclax and a CD20 antibody (rituximab or, if applicable, ofatumumab) are eligible to participate in the study. At least 12 months must have elapsed between the end of first-line therapy and the recurrence requiring treatment. No other therapy for CLL may have been administered between first-line therapy and study enrollment.