An Independent Data Monitoring Committee (IDMC) recommended that a phase 3 study be stopped early after data indicated that Imbruvica™ (ibrutinib) provided a clear survival advantage compared with the control drug in patients with chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. The American Cancer Society estimates that approximately 15,000 people will be diagnosed with CLL this year. Currently, there are approximately 95,000 people in the United States living with CLL.
CLL is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells that exist in two forms: B- and T-cells. These cells are produced in the bone marrow and each serves a specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal. B-lymphocytes accumulate in the blood, bone marrow, lymph nodes, and spleen. This results in overcrowding of these areas and suppression of the formation and function of blood and immune cells. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further reduction in the body’s ability to fight infection.
Imbruvica is a selective inhibitor of Bruton’s tyrosine kinase, a component of the B-cell receptor signaling pathway that plays a key role in the development and progression of CLL. In other words, the targeted therapy attacks the pathway that mediates disease progression.
The RESONATE study is an international, randomized, open-label Phase 3 clinical study that includes 391 patients with relapsed or refractory CLL/SLL with measurable nodal disease and who were not eligible for treatment with purine analog-based therapy, who had received at least one prior therapy. Patients were randomized to receive oral Imbruvica once daily or intravenous doses of Arzerra® (ofatumumab) over the course of 24 weeks. Both treatments were administered until disease progression or unacceptable toxicity. The primary endpoint of the study is progression-free survival (PFS) and one of the key secondary endpoints is overall survival (OS).
It is common practice for independent monitoring committees to conduct interim analyses of clinical trials. They can either recommend the study continue as planned or be stopped early due to safety concerns or because data shows the study drug will clearly succeed in meeting the goals of the trial.
In this case, the IDMC unanimously recommended stopping the study early based on a planned interim analysis—because they observed statistically significant differences in PFS and OS. The IDMC concluded that these results suggest evidence of clinical benefit as well as a tolerable safety profile in patients receiving Imbruvica as compared to Arzerra. What’s more, the IDMC also recommended that the study sponsor provide access to Imbruvica for all patients in the study.
Imbruvica is currently FDA-approved for the treatment of mantle cell lymphoma and has received the FDA’s new breakthrough therapy designation given to experimental drugs deemed to be potentially important advances in treating serious diseases. The early end to this study may pave the way for expanded approval for the treatment of CLL.
The results of this study will be presented at an upcoming medical meeting and also submitted for publication in a peer-reviewed journal.
Independent Data Monitoring Committee Recommends Early Stopping of Phase 3 Study of Ibrutinib in Relapsed/Refractory CLL/SLL Patients Based on a Planned Interim Analysis. Janssen Research & Development, LLC News Release. Available at: http://www.jnj.com/news/all/Independent-Data-Monitoring-Committee-Recommends-Early-Stopping-of-Phase-3-Study-of-Ibrutinib-in-Relapsed-Refractory-CLL-SLL-Patients-Based-on-a-Planned-Interim-Analysis