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Media Release | Cologne, 27 May 2013
Phase III data from the CLL11 study to be presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO):
The German CLL Study Group (GCLLSG) today announced the first results from CLL11, a phase III study which is being conducted in collaboration with Hoffmann-La Roche. The CLL11 study compared the combination of either GA101 or rituximab and chlorambucil, a standard chemotherapy, to chlorambucil alone in elderly patients with chronic lymphocytic leukemia (CLL). CLL is one of the most common forms of blood cancer and the majority of patients diagnosed with this disease are of advanced age. Many of these have concurrent diseases and therefore may not tolerate more aggressive therapy which is the standard in younger patients. The CLL11 study included elderly people with previously untreated CLL and coexisting medical conditions (comorbidities).
“So far, conclusive evidence that treatments currently available for elderly CLL patients with comorbidities are superior to chlorambucil monotherapy has been lacking. This is the first direct comparison of chlorambucil monotherapy to a combination regimen of chlorambucil plus GA101 or rituximab”, said Dr Valentin Goede, a hematologist of the GCLLSG and the Principal Investigator of the CLL11 trial. “Based on the results we have seen, elderly CLL patients with comorbidities and treated with chlorambucil should also receive a CD20 antibody to improve the outcomes of their treatment”.
GA101 combined with chlorambucil demonstrated a significant 86% reduction in the risk of disease progression, relapse or death. Additionally, the length of time during which people lived without their disease worsening (median progression-free survival, PFS) was more than doubled (23 months compared to 10.9 months, HR=0.14, 95% CI 0.09-0.21, p <.0001) when compared to chlorambucil alone. Rituximab combined with chlorambucil demonstrated a significant 68% reduction in the risk of disease progression, relapse or death. The PFS was significantly increased (15.8 months compared to 10.8 months, HR=0.32, 95% CI 0.24-0.44, p <.0001) when compared to chlorambucil alone.
“To draw final conclusions on the efficacy and safety of combined treatment with GA101 with chlorambucil relative to rituximab plus chlorambucil in this particular patient population, results of the comparison of the two antibody arms of the CLL11 study will be important. These will be available soon,” said Prof Michael Hallek, Director of the Department I of Internal Medicine at the University Hospital Cologne and Head of the GCLLSG.
Founded in 1996 and headed by Prof Dr Michael Hallek, the GCLLSG has been running various phase III, phase II, and phase I trials in CLL with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 trial which led to the current standard of care in CLL. For many years, GCLLSG has been aiming to improve not just the treatment of younger and physically fit patients, but also that of elderly and less fit patients. These patients are generally underrepresented in clinical trials although they significantly contribute to the population of CLL patients treated by doctors in daily practice. The German CLL Study Group is an independent non-profit research organization supported by the Deutsche Krebshilfe.
CLL11 is a phase III, multicenter, open-label, randomized three-arm study investigating the safety and efficacy profile of either GA101 added to chlorambucil or rituximab added to chlorambucil compared to chlorambucil alone in 781 previously untreated people with CLL and comorbidities (589 patients are included in this analysis and an additional 192 patients have been enrolled to enable the forthcoming direct comparison of GA101 versus rituximab both in combination with chlorambucil). The study was conducted by the German CLL Study Group (GCLLSG) in collaboration with Hoffmann-La Roche. The primary endpoint of the study was PFS with secondary endpoints including overall response rate (ORR), overall survival (OS), disease-free survival (DFS), minimal residual disease (MRD) and safety profile. Specifically, the CLL11 trial data to be presented during ASCO showed the following:
Table 1: Summary of key efficacy and safety data
Total Stage 1 N = 589 |
Stage 1a | Stage1b | ||
| Clb (N=118)* |
GA101 + Clb (N=238) |
Clb (N=118)* |
Rituximab+ Clb (N=233) |
|
| Median observation time, months | 13.6 | 14.5 | 14.2 | 15.3 |
| End of treatment response rate, % | 30.2 | 75.5 | 30.0 | 65.9 |
| Complete responses, % | 0 | 22.2 | 0 | 8.3 |
| Median PFS, months | 10.9 | 23.0** | 10.8 | 15.7 |
| HR, CI, p-value | 0.14, 0.09-0.21, <.0001 | 0.32, 0.24-0.44, <.0001 | ||
| Minimal Residual Disease negative in blood | 0% | 31% | 0% | 2% |
| Grade 3-4 adverse events during treatment, % | 41 | 67 | 41 | 46 |
| Infusion-related reaction | - | 21*** | - | 4 |
| Neutropenia | 15 | 34 | 15 | 25 |
| Infections | 11 | 6 | 11 | 8 |
| * In the chlorambucil-only arm, data cut-off times were different for the two independent combination arms which lead to the slightly different results in the efficacy outcomes presented above. ** The percentage of GA101 patients who have not progressed and who have been observed for longer than the current median PFS time is very small (less than 10%) and therefore as observation time increases, future calculations of median PFS for the GA101 patients are likely to report different results. *** No serious (grade 3/4) IRRs have been reported beyond the first infusion. |
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