NCT06757647

Acalabrutinib for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Prospective Phase 2 Study of the Effect of Acalabrutinib on Myocardium on Ibrutinib Exposed Patients With CLL

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 61 (estimated)
• Sponsor: Seema Bhat · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well acalabrutinib works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and evaluates how treatment with acalabrutinib affects heart function. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. CLL/SLL patients treated with a different BTK inhibitor called ibrutinib often experience cardiac side effects, leading to discontinuation of life-saving therapy. Treatment with acalabrutinib after discontinuing, or even before starting, treatment with ibrutinib may reverse or prevent cardiac side effects and be an effective treatment option for patients with CLL/SLL.

Detailed description

PRIMARY OBJECTIVE: I. To determine cardiac magnetic resonance imaging (MRI) changes over time in patients with CLL who are intolerant to ibrutinib and switch to acalabrutinib therapy. SECONDARY OBJECTIVES: I. To determine the rate of recurrence of \>= grade 2 adverse events (AEs) causing ibrutinib intolerance at 1 year when patients with CLL/SLL are treated with acalabrutinib. II. To determine the response rates which include (complete response \[CR\], partial response \[PR\], PR with lymphocytosis). III. To determine C481S/PLCG2 mutation free (defined 0 mutation bearing alleles) and clinical progression free survival at 3 years. IV. To assess atrial fibrillation (AF) rates at 12 months post acalabrutinib transition. EXPLORATORY OBJECTIVES: I. To determine cardiac injury (i.e., troponin-TnT and N-terminal pro B-type natriuretic peptide \[NT-proBNP\]), C-reactive protein (CRP), and pro-inflammatory (ex. interleukin \[IL\]-6, IL-17, and tumor necrosis factor \[TNF\]-α, etc.) biomarkers. II. To assess fibrosis, serum procollagen type I carboxy-terminal propeptide (PICP), galectin-3, transforming growth factor (TGF)-β1, and matrix metalloproteinases (MMPs)-2, and -7 will be collected and measured at each timepoint. III. To determine cardiac magnetic resonance imaging (CMR) imaging changes that may be induced by acalabrutinib over time in BTK naive patients. OUTLINE: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CMR, computed tomography (CT), bone marrow aspiration/biopsy, and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 6 months for up to 10 years.

Conditions

• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	Acalabrutinib	Given PO
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging of the Heart	Undergo CMR

Timeline

• Start date: 2025-05-27
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2025-01-03
• Last updated: 2025-12-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study