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

NCT06757647 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-23058NCI-2024-10481
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Cardiac magnetic resonance imaging changes

  The cardiac MRI changes that will be assessed include Extracellular volume (ECV), Native T1, and T2, where changes in ECV from baseline to 3-month post acalabrutinib initiation would be the primary endpoint

  Baseline to 3-month post acalabrutinib initiation

Secondary Outcomes (5)

• Overall response rate (ORR)

  At the end of cycle 24 (1 cycle = 28 days)

• Clinical progression free survival (PFS)

  From start of study treatment until first progression or death, assessed at 3 years

• C481S/PLCG2 mutation free survival

  At 3 years

• Incidence of recurrence of grade 2 or greater adverse events (AEs) that previously led to ibrutinib intolerance

  During the first 12 cycles of single agent acalabrutinib (1 cycle = 28 days)

• Atrial fibrillation (AF) rates

  At 12 months post acalabrutinib transition

Study Arms (1)

Treatment (acalabrutinib)

EXPERIMENTAL

Patients receive acalabrutinib PO 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, CT, bone marrow aspiration/biopsy, and collection of blood samples throughout the trial.

Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging of the Heart

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP 196, ACP-196, ACP196, Bruton Tyrosine Kinase Inhibitor ACP-196

Treatment (acalabrutinib)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (acalabrutinib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (acalabrutinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (acalabrutinib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (acalabrutinib)

Magnetic Resonance Imaging of the Heart PROCEDURE

Undergo CMR

Also known as: Cardiac MRI, Heart MRI

Treatment (acalabrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women \>= 18 years of age
• Diagnosis of CLL/SLL meeting criteria as defined by International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2018 criteria
• CLL patients cardiac intolerant to current treatment with ibrutinib as defined by AF or other cardiac arrhythmias. Other ibrutinib-related intolerances will be excluded
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (Independent of growth factor support at screening unless due to marrow involvement by CLL/SLL and/or disease-related immune thrombocytopenia. If cytopenias are due to disease in the bone marrow any degree of cytopenias is allowed. Patients with active uncontrolled autoimmune cytopenias are excluded)
• Platelets \>= 30,000/mm\^3 (Independent of growth factor support at screening unless due to marrow involvement by CLL/SLL and/or disease-related immune thrombocytopenia. If cytopenias are due to disease in the bone marrow any degree of cytopenias is allowed. Patients with active uncontrolled autoimmune cytopenias are excluded)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (excepting Gilbert's syndrome) (at screening)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN (at screening)
• Creatinine clearance \>= 30 mL/min/1.73m\^2 (at screening)
• Using 24-hour creatinine clearance or modified Cockcroft-Gault equation
• Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib
• Willing and able to participate in all required evaluations and procedures in this study protocol
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

You may not qualify if:

• Prior exposure to acalabrutinib for primary cohort and prior exposure to BTK inhibitor for pilot cohort
• Presence of C481S mutation or PCLG2 mutation
• Disease progression on ibrutinib
• History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
• Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study
• Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for \>= 3 years without further treatment
• Clinically significant cardiovascular disease such as prior myocarditis, congestive heart failure, prior documented myocardial infarction (i.e., not self-reported), known infiltrative cardiomyopathy (ex. cardiac sarcoidosis, cardiac amyloidosis, etc.) or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll on study
• Prior allogeneic stem cell transplantation
• Prior cardiac transplantation
• Systemic or non-cancer targeted anti-inflammatory medications (i.e., steroids)
• Contradictions to MRI: non-compatible metal implant, weight \> 300 pounds (lbs.) (MRI scanner limit), severe claustrophobia, advanced or end-stage renal disease (ESRD) (contraindication to gadolinium), pregnancy, cognitive disabilities that may impair ability to comply with instructions or provide informed consent
• Has difficulty with or is unable to swallow oral medication or has significant. gastrointestinal disease that would limit absorption of oral medication
• Known history of infection with HIV or any active significant infection (e.g., bacterial, viral, or fungal) including subjects with positive cytomegalovirus \[CMV\] deoxyribonucleic acid \[DNA\] polymerase chain reaction \[PCR\])
• Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components
• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)

Sponsors & Collaborators

• Seema Bhat: lead
• Acerta Pharma, LLC: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; Specimen Handling; Biopsy

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Seema A Bhat, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 27, 2024
• First Posted: January 3, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

US (1)