NCT04178798

Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Chronic Lymphocytic Leukemia

Completed Phase 3 Last updated 17 March 2025

What this trial tests

Phase 3 trial testing Acalabrutinib 100 MG Oral Capsule in Chronic Lymphocytic Leukemia- Binet Staging System in 22 participants. Completed in 3 December 2024.

Timeline

9 December 2019

Primary endpoint
3 December 2024

3 December 2024

Quick facts

Lead sponsor	PETHEMA Foundation
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	22
Start date	9 December 2019
Primary completion	3 December 2024
Estimated completion	3 December 2024
Sites	8 locations across Spain

Drugs / interventions tested

• Acalabrutinib 100 MG Oral Capsule — full drug profile →

Conditions studied

• Chronic Lymphocytic Leukemia- Binet Staging System — all drugs for Chronic Lymphocytic Leukemia- Binet Staging System →

Sponsor

PETHEMA Foundation

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia- Binet Staging System. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies.
   Abbas HA, Wierda WG. · · 2021 · cited 30× · PMID 34055635 · DOI 10.3389/fonc.2021.668162
2. The Role of BTK Inhibition in the Treatment of Chronic Lymphocytic Leukemia: A Clinical View.
   Tambaro FP, De Novellis D, Wierda WG. · · 2021 · cited 17× · PMID 34744463 · DOI 10.2147/jep.s265284
3. The importance of <i>TP53</i> status in cancer therapy: The example of chronic lymphocytic leukemia.
   Mirgayazova R, Khadiullina R, Gilyazova E, Davletshin D, et al · · 2025 · cited 1× · PMID 40321704 · DOI 10.22099/mbrc.2025.51477.2054