Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Chronic Lymphocytic Leukemia
Status:
Recruiting
Trial end date:
2024-10-01
Target enrollment:
Participant gender:
Summary
Study Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of
Patients with Early Stage CLL With High Risk of Early Disease Progression.
The study will consist of a screening phase, a treat¬ment/observation phase until
progression, and a follow-up phase for progression in patients who discontinue treatment with
Acalabrutinib without confirmed progression. Patients who progress will be followed for
survival and initiation of subsequent antileukemic therapy. In the study, 130 patients from
20 centers in Spain with intermediate, high or very high risk will be randomized (1:1) to
receive Acalabrutinib (n=65) or clinical observation (n=65). Acalabrutinib will be
administered orally 100 mg twice daily on a continuous schedule.
Even though the majority of patients with CLL are currently diagnosed at early stages of the
disease, there is a consensus that the standard of care in these patients is clinical
observation (watch & wait) despite of the presence of risk factors for premature disease
progression. Early treatment in patients with adverse prognostic parameters could prevent a
disease evolving to a more advanced stage, and therefore more difficult to treat. So far,
conventional chemotherapy did not show any benefit in terms of overall survival in patients
with early stage CLL. (Dighiero 1998, Hoechstetter Leukemia 2017) Alongside this, treatment
with chemotherapy may provoke two undesired effects: first, the occurrence of bone marrow
toxicity that may hamper the subsequent administration of other treatments during the course
of the disease; second, but not less relevant, genotoxic drug delivery may elicit a
phenomenon of clonal selection leading to the appearance of CLL cells with genetic
aberrations associated with refractoriness and aggressive outcome (i.e., TP53).
Against this background, it is of interest to investigate the role of new non-genotoxic drugs
in the treatment of patients with CLL in early stages. Among different scores for selecting
cases that are likely to progress rapidly, the German CLL Study Group (GCLLSG) risk score
that includes 8 independent predictors for OS and PFS, differentiates patients with low-risk
PFS vs. those with risk of early disease progression (median PFS 87 months vs. less than 27
months), allowing for a risk-adapted treatment approach in early stage CLL. (Pflug 2014,
Langerbeins 2015).
Acalabrutinib, a second-generation, selective inhibitor of BTK, has shown substantial
activity in patients with CLL. Acalabrutinib is a non-genotoxic drug active in cases with
genetic lesions associated with chemorefratoriness and adverse outcome, including patients
with alterations of TP53. Therefore, acalabrutinib represents a suitable compound for the
treatment of patients with CLL in early stages with risk of early disease progression,
including the high-risk CLL patient population with TP53 alterations.