A Prospective Observational Trial to Assess Treatment Sequences and Factors That Impact Overall Sur-vival in Patients With Chronic Lymphocytic Leukaemia (CLL) Treated Within First-line Studies of the GCLLSG

Primary objective:

To assess the overall survival (OS) from initiation of first-line treatment in patients who received different first-line therapies within the CLL13, CLL14, or CLL17 clinical trials.

Rationale for primary objective:

CLL is the most common leukaemia in adults in the western countries with an age-standardized incidence between 4 and 5 cases per 100,000 person-years and about 5,500 new CLL cases in Germany1. The clinical course of CLL is highly variable and can be predicted by clinical staging (according to Rai and Binet2,3) as well as genetic4, serum and other markers. Due to the increasing effectiveness of approved first-line therapies, some patients with CLL experience a normal life expectancy. Therefore, the total duration of clinical trials would need to be enormously extended in order to capture data on OS which is operationally not practicable. Moreover, a number of effective treatment options are available for follow-up therapies. Hence, the analysis of OS might not only be affected by the choice of first-line therapy but also by subsequent therapies and other competing factors that should be collected. Studies on long-term survival of patients with CLL have primarily relied on registry data5 and population-based studies6 and were conducted outside of clinical trials. These studies only occasionally consider specific comorbidities7,8, are retrospective in nature9, and often have limited observation periods. In addition, a potential accrual bias may be difficult to address within the format of registry data collection.

Prospective follow-up of patients would enable more comprehensive analyses within a predefined study patient population. This observational trial aims to prospectively analyze OS for a predefined study population. Patients who received first-line treatment in CLL1310, CLL1411, or CLL17 trials conducted by the German CLL Study group (GCLLSG) will be included to carry out this comprehensive analysis of OS in a well-defined patient population. To capture OS, all data that could influence OS, including but not limited to the presence of genomic risk factors and concomitant conditions at different time points, age, sex, country, subsequent lines of therapy and the occurrence of other diseases including causes of death, will also be recorded. In addition, data that had been collected within the initial first-line studies will be included in the analyses.