Inclusion Criteria:

          -  Subject must be able to voluntarily sign and date an informed consent, approved by an
             Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the
             initiation of any screening or study specific procedures.

          -  The time from diagnosis to consent should be ≤6 months.

          -  Subject must be ≥ 18 years of age.

          -  Subject must have diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines.

          -  Rai stage 0-2 disease without indication for treatment as defined by the 2018 iwCLL
             guidelines

          -  Subject must have high risk CLL as defined by any one of the following:

               -  NOTCH1 mutated (classic frameshift mutation only)

               -  Unmutated V4-39 B cell receptor usage

               -  Pathogenic c-MYC mutations

               -  Complex karyotype, (by CpG/oligodeoxynucleotide stimulation)

               -  Deletion 17p, or presence of TP53 mutation

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.

          -  PT/PTT/INR within 1.5 x the ULN

          -  Adequate renal function defined by serum creatinine less than 2 x ULN

          -  Adequate hepatic function:

               -  ALT/AST less than 2x ULN

               -  Tbili less than 1.5 X ULN unless bilirubin elevation is due to Gilbert's syndrome
                  (total bilirubin <3)

          -  Subject must have adequate bone marrow function.

               -  Absolute neutrophil count ≥1.0 x103/μL

               -  Hemoglobin ≥ 11.0 g/dL

               -  Platelets ≥ 100 x 103/μL

        Exclusion Criteria:

          -  Previous exposure to any systemic anti-cancer therapy as a treatment for CLL,
             including but not limited to chemotherapy, immunotherapy, radiotherapy, or
             investigational therapy. Note, patients treated with chemotherapy for a prior
             non-hematologic malignancy if more than 5 years earlier are eligible.

          -  Subject with a history of malignancy except for non-melanoma skin cancers. Subjects
             treated with curative intent via methods of local resection and or locally targeted
             anticancer treatment and are free of malignancy for at least 5 years from treatment
             end will be allowed to enroll.

          -  Subject requires chronic immunosuppressive therapy for any reason or was treated with
             immunosuppressive therapy within 6 months of study entry.

          -  Subjects with a history of autoimmune hemolytic anemia or immune thrombocytopenia
             purpura.

          -  Subject has prolymphocytic leukemia.

          -  Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand
             disease)

          -  Subject requires warfarin or equivalent vitamin K antagonist

          -  Uncontrolled or active significant infection,

          -  History of or suspected or confirmed PML

          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
             screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart
             Association Functional Classification. Subjects with controlled, asymptomatic atrial
             fibrillation during screening can enroll on study.

          -  Patients with stroke or CNS hemorrhage within 6 months

          -  Pregnant or breastfeeding

               -  Women of childbearing potential (WCBP) who are sexually active with heterosexual
                  partners must agree to use highly effective methods of contraception during
                  treatment and for 2 days after the last dose of acalabrutinib.

          -  Major surgical procedure within 28 days of first dose of study drug. If a subject had
             surgery, they must have recovered adequately from any toxicity or complications before
             the first dose of study drug.

          -  Has difficulty with or is unable to swallow oral medication or has significant
             gastrointestinal disease that would limit absorption of oral medication.

          -  Subject is known to be positive for human immunodeficiency virus (HIV)

          -  Active hepatitis C, as confirmed by being positive for Hep C RNA by PCR

          -  Active hepatitis B infection documented by a positive PCR for Hep B DNA. If hepatitis
             B serology is positive for hepatitis B core antibody, but Hep B DNA PCR is negative,
             patient is eligible to enroll.

          -  Subject requires strong CYP 3A4/5 inhibitors or inducers (Appendix B).

          -  Subject requires proton pump inhibitors. (Subjects that can transition to an H2
             antagonist are allowed to enroll.)