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Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT06757647

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

A Phase 2 study testing Acalabrutinib, Biospecimen Collection and Bone Marrow Aspiration in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by Seema Bhat at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib, Biospecimen Collection and Bone Marrow Aspiration
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteUnited States
Study dates
27 May 2025to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
Show all 31Show fewer
  • 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)
  • Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
  • Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
  • Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
  • Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x ULN
  • Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
  • History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
  • Major surgical procedure within 28 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
  • Received a live virus vaccination within 28 days of first dose of study drug
  • History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
  • Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
  • Hepatitis B or C serologic status:
  • Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded
  • Breastfeeding or pregnant
  • Concurrent participation in another therapeutic clinical trial

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Seema A. Bhat, MD, 614-293-3196, Seema.Bhat@osumc.edu

    Seema A. Bhat, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Acalabrutinib, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called ACP 196, ACP-196, ACP196, Bruton Tyrosine Kinase Inhibitor ACP-196

    Given PO

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance Imaging of the HeartProcedure or surgery

    Also called Cardiac MRI, Heart MRI

    Undergo CMR

Study groups in NCT06757647
Study groupRoleWhat they receive
Treatment (acalabrutinib)ExperimentalPatients 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.
Receives: Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging of the Heart

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Baseline to 3-month post acalabrutinib initiation

Secondary outcomes (5)

  1. Overall response rate (ORR)

    ORR will be defined as the number of patients with a response (complete response [CR], partial response [PR], PR with lymphocytosis) divided by the number of eligible patients who start study treatment. Response rates including CR and ORR will be estimated at the end of treatment and at various time points with exact 95% confidence intervals. The change in response over time will be presented in a descriptive manner as well as graphically through use of a Sankey plot.

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

  2. Clinical progression free survival (PFS)

    PFS will be described using the method of Kaplan-Meier and estimates at 3 years will be provided with 95% confidence intervals.

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

  3. C481S/PLCG2 mutation free survival

    Mutation free survival will be described using the method of Kaplan-Meier and estimates at 3 years will be provided with 95% confidence intervals.

    Measured: At 3 years

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

    The recurrence rate will be calculated as the number of patients who have recurrence (grade 2 or higher) of the AE that previously led to ibrutinib intolerance during the first 12 cycles of single agent acalabrutinib therapy divided by the number of eligible patients who start acalabrutinib therapy. The rate of recurrence of grade 2 or greater AEs will be analyzed using an exact binomial test for a single proportion and will be estimated with exact 95% confidence intervals.

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

  5. Atrial fibrillation (AF) rates

    AF rates will be calculated as the number of patients having AF (any grade) during the first 12 cycles of single agent acalabrutinib divided by the number of eligible patients who start acalabrutinib therapy.

    Measured: At 12 months post acalabrutinib transition

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2025
  2. Study start27 May 2025
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06757647
Sponsor's protocol ID
OSU-23058
Other IDs
NCI-2024-10481
Status last verified
Dec 2025
First submitted
27 Dec 2024
Last updated
16 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib, Biospecimen Collection and Bone Marrow Aspiration in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by Seema Bhat at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cardiac magnetic resonance imaging changes (time frame: Baseline to 3-month post acalabrutinib initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06757647.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2025.

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