Clinical Trial Spotlight: Trial 14-296: A Phase 2 Study of Ibrutinib Plus FCR for Previously Untreated Younger Patients With Chronic Lymphocytic Leukemia

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Written By

Matthew Davids, MD, MMSc


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Recently, long-term follow-up on chronic lymphocytic leukemia (CLL) patients treated with the chemoimmunotherapy regimen fludarabine, cyclophosphamide, rituximab (FCR) demonstrated that a substantial subset of these patients with lower-risk disease can achieve prolonged disease-free survival. The BTK inhibitor ibrutinib (Imbruvica) was recently FDA-approved as a single agent for frontline therapy of CLL, and it is highly active across all CLL subsets, including high-risk disease. Yet, ibrutinib monotherapy usually leads to only partial responses, requiring patients to stay on indefinite therapy. In this investigator-initiated clinical trial, we hypothesized that combining ibrutinib with FCR (iFCR) for younger patients with previously untreated CLL would result in deeper responses that would allow for durable remissions even in patients with higher risk disease, and potentially obviate the need for continuous ibrutinib therapy.

In the first phase of the trial, we treated 35 patients with iFCR, and in an interim analysis presented at the 2016 ASH Annual Meeting we reported that 89% of patients achieved minimal residual disease (MRD) negativity in the bone marrow, significantly higher than the approximately 20-30% rate seen historically with FCR alone. The toxicity profile of iFCR has been favorable, with low rates of hematologic and infectious toxicities compared to prior studies of FCR alone, likely due to the focus on a younger population and the requirements for mandatory growth factor support and antimicrobial prophylaxis on this study.


Based on these promising initial results, we recently opened a 50-patient expansion cohort to further explore whether a time-limited course of 6 months of iFCR plus 2 years of ibrutinib monotherapy maintenance can provide durable remission without the need for indefinite therapy in patients who achieve bone marrow MRD-negativity (see schema above). Eligible patients are those age 65 or younger with previously untreated CLL who do not have deletion 17p or TP53 mutation. This study is actively accruing, and we would be grateful to see in consultation any potentially eligible patients who may be willing to participate in this or other studies.

For more information about this study, call 617-632-6331 or email