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

Recruiting now · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

In brief

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.

Key facts

Study ID: NCT06757647
Run by: Seema Bhat
People needed: 61
Starts: 2025-05-27
Expected to finish: 2027-12-31
Last updated by the study team: 2025-12-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
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)

Where it is running

Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.