Inclusion Criteria:

          1. Men and women ≥ 18 years of age with a confirmed diagnosis of CLL/SLL, which has
             relapsed after, or been refractory to, ≥ 2 previous treatments for CLL/SLL.

          2. Must have measurable CLL/SLL defined as ≥ 1 lymph node ≥ 2 cm as measured in the
             longest diameter.

          3. Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring
             treatment:

               1. Evidence of progressive marrow failure as manifested by the development of, or
                  worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets <
                  100,000/μL).

               2. Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic
                  splenomegaly.

               3. Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or
                  symptomatic lymphadenopathy.

               4. Progressive lymphocytosis with an increase of > 50% over a 2-month period or a
                  lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear
                  regression extrapolation of absolute lymphocyte counts (ALC) obtained at
                  intervals of 2 weeks over an observation period of 2 to 3 months. In subjects
                  with initial blood lymphocyte counts of < 30 X 109/L (30,000/μL), LDT should not
                  be used as a single parameter to define indication for treatment. In addition,
                  factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g.,
                  infections) should be excluded.

               5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard
                  therapy.

               6. Constitutional symptoms documented in the subject's chart with supportive
                  objective measures, as appropriate, defined as ≥ 1 of the following
                  disease-related symptoms or signs:

             i. Unintentional weight loss ≥ 10% within the previous 6 months before Screening.

             ii. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without
             evidence of infection.

             iii. Night sweats for > 1 month before Screening without evidence of infection.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

          5. Agreement to use highly effective methods of contraception during the study and for 2
             days after the last dose of study drug if sexually active and able to bear or beget
             children (see Section 3.7.9 for list of highly effective methods of contraception).

          6. Willing and able to participate in all required evaluations and procedures in this
             study protocol including swallowing capsules without difficulty.

          7. Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information (in accordance
             with national and local subject privacy regulations).

          8. Removed at Amendment 11.

        Inclusion Criteria for Treatment Subgroups

          1. Treatment Naive only: Men and women ≥ 18 years of age with confirmed diagnosis of
             CLL/SLL, who require treatment per National Cancer Institute (NCI) or International
             Working Group guidelines and a) do not want to receive chemoimmunotherapy or b) have
             comorbidities that would preclude chemoimmunotherapy.

          2. Ibrutinib Intolerant only: Men and women ≥ 18 years of age with confirmed diagnosis of
             CLL/SLL who are not tolerating ibrutinib due to ibrutinib-related AEs.

          3. Richter's Syndrome/Prolymphocytic Leukemia Transformation only: Men and women ≥ 18
             years of age and biopsy proven diffuse large B cell lymphoma (DLBCL) Richter's
             transformation or prolymphocytic leukemia transformation.

          4. Ibrutinib R/R only: Men and women ≥ 18 years of age with confirmed diagnosis of
             CLL/SLL whose best response after 2 cycles of ibrutinib therapy was SD or nonresponse
             or who initially responded to ibrutinib therapy and now have signs of clinical
             progression.

        Exclusion Criteria:

          1. Prior malignancy, except for adequately treated basal cell, squamous cell skin cancer
             or in situ cervical cancer. Subjects with other prior malignancies from which the
             subject has been disease free for ≥ 2 years may be included if approved by the medical
             monitor.

          2. A life-threatening illness, medical condition or organ system dysfunction which, in
             the investigator's opinion, could compromise the subject's safety, interfere with the
             absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.

          3. 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, or left ventricular ejection fraction (LVEF) ≤ 40%.

          4. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel, symptomatic inflammatory bowel disease,
             partial or complete bowel obstruction, or gastric restrictions and bariatric surgery,
             such as gastric bypass.

          5. Any immunotherapy within 4 weeks of first dose of study drug.

          6. For subjects with recent chemotherapy or experimental therapy the first dose of study
             drug must occur after 5 times the half-life of the agent(s).

          7. Relapsed after, or refractory to, prior BTK inhibitor therapy (Note: Does not apply to
             Ibrutinib R/R or Richter's Syndrome Group).

          8. Any history of Richter's transformation (Note: Does not apply to Richter's Syndrome
             Group).

        10. Central nervous system (CNS) involvement by lymphoma. 11. Grade ≥ 2 toxicity (other
        than alopecia) continuing from prior anticancer therapy including radiation.

        12. Known history of human immunodeficiency virus (HIV) or serologic status indicating
        active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection or any uncontrolled
        active systemic infection. Subjects with hepatitis B core antibody positive who are surface
        antigen negative or who are hepatitis C antibody positive will need to have a negative
        polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface
        antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive
        will be excluded.

        13. Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to
        autoimmune destruction within the screening period or requirement for high doses of
        steroids (> 20 mg daily of prednisone daily or equivalent).

        14. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of
        study drug.

        15. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole,
        lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).

        16. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.,
        phenprocoumon) within 7 days of first dose of study drug.

        17. Major surgery within 4 weeks before first dose of study drug. 18. ANC < 0.75 x 109/L or
        platelet count < 50 x 109/L unless there is bone marrow involvement.

        19. Total bilirubin > 1.5 x ULN (total bilirubin ≤ 2.5 x ULN allowed in subjects with
        autoimmune hemolytic anemia that is otherwise controlled); and aspartate aminotransferase
        (AST) or alanine aminotransferase (ALT) > 3.0 x ULN unless disease related.

        20. Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN. 21. Significant screening ECG
        abnormalities including, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher
        bradycardia, or QTc ≥ 480 ms.

        22. Cardiac troponin I levels above the limit of normal as specified by the manufacturer.

        23. Breast feeding or pregnant. 24. History of bleeding diathesis (e.g., hemophilia, von
        Willebrand disease). 25. Concurrent participation in another therapeutic clinical trial.
        26. Estimated creatinine clearance of < 30 mL/min, calculated using the formula of
        Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if
        female].

        27. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before
        screening.