Inclusion Criteria:

          1. Written informed consent obtained to participate in the study and HIPAA authorization
             for release of personal health information.

          2. Age ≥18 years at the time of consent.

          3. Subject has adequate performance status as defined by ECOG of ≤ 2. (Note: Performance
             status can be assessed after administration of corticosteroids.)

          4. Subject has histological confirmation of biopsy-proven CNS lymphoma OR MRI findings
             consistent with CNS lymphoma if biopsy is not possible (due to inaccessible location).
             Subjects with intra-ocular lymphoma will not be excluded as long as there is also
             parenchymal disease.

          5. Subject has B-cell Non-Hodgkin Lymphoma.

          6. Subject has no evidence of systemic involvement of lymphoma confirmed by CT or PET-CT
             imaging within 28 days prior to first dosing in the study.

          7. Subject must have received at least one prior line of chemotherapy for primary or
             secondary CNS lymphoma. There is no limit on the number of prior treatment regimens.

          8. Subject has adequate organ function as demonstrated by: System Laboratory Value
             Hematological* Absolute Neutrophil Count (ANC) ≥ 1 x 109/L Platelets ≥ 75 x 109/L
             Renal* Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula
             (Appendix B) Hepatic* Bilirubin ≤ 1.5 × upper limit of normal (ULN). Subjects with
             Gilbert's syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their
             conjugated bilirubin is <1.5× ULN) Aspartate aminotransferase (AST) ≤ 2.5 × ULN
             Alanine aminotransferase (ALT) ≤ 2.5 × ULN Coagulation International Normalized Ratio
             (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤ 2 ×
             ULN (in the absence of lupus anticoagulant)

          9. Subject is able to receive isavuconazole for prophylaxis of invasive aspergillosis
             while subject receives acalabrutinib therapy.

         10. Female subjects of childbearing potential must have a negative serum pregnancy test
             within three days (72 hours) prior to initiating study treatment. Note: Females are
             considered of childbearing potential unless they are surgically sterile (have
             undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they
             are naturally postmenopausal for at least 12 consecutive months. Documentation of
             postmenopausal status must be provided.

        10. Females of childbearing potential must be willing to abstain from heterosexual activity
        or to use 2 forms of effective methods of contraception from the time of informed consent
        until 2 days after the last dose of acalabrutinib. The two contraception methods can be
        comprised of two barrier methods, or a barrier method plus a hormonal method.

        Exclusion Criteria:

        1. Subjects meeting any of the following exclusion criteria will not be able to participate
        in this study 2.Prior cancer treatment that was completed less than 14 days prior to Day 1
        of study dosing or if subject has not recovered from all reversible acute toxic effects of
        the regimen to grade ≤1 or baseline.

        3. Prior brain radiotherapy under the following conditions:

          -  Whole-brain radiotherapy (WBRT) that was completed less than 28 days prior to Day 1 of
             study dosing

          -  Stereotactic radiosurgery (SRS) that was competed less than 14 days prior to Day 1 of
             study dosing.

             3. Currently participating in or has participated in a study of an investigational
             agent within 28 days of first dosing with study treatment.

             4.Subject is pregnant or breastfeeding (Note: breast milk cannot be stored for future
             use while the mother is being treated on study).

             5 Subject has a known additional malignancy that is active and/or progressive
             requiring treatment; exceptions include basal cell or squamous cell skin cancer, in
             situ cervical or bladder cancer, or other cancer for which the subject has been
             disease-free for at least five years.

             6. Subject has active CSF involvement that requires ongoing intrathecal chemotherapy.

             7. Previous exposure to a BTK inhibitor. 8. Subjects with severe hepatic
             insufficiency, as defined by Child-Pugh Score > 6 (Appendix C).

             9. Subject is receiving prohibited medications or treatments as listed in Section 5.3
             of the protocol that cannot be discontinued/replaced by an alternative therapy.
             Subject requires treatment with a strong cytochrome P450 3A4 (CYP3A4)
             inhibitor/inducer other than isavuconazole (please consult Section 5.3). Subjects may
             be eligible if they are medically able to discontinue CYP3A4 inhibitors/inducers at
             least 14 days before the first dose of study treatment.

             10. Subject requires or receiving anticoagulation with warfarin or equivalent vitamin
             K antagonists (e.g., phenprocoumon) within 14 days of first dose of study drug.
             Subjects requires or is taking direct oral anticoagulants (e.g. apixaban, rivaroxaban,
             edoxaban, lovenox) within 7 days of first dose of study drug.

             11. Subject requires treatment with proton pump inhibitors (e.g., omeprazole,
             esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects
             receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are
             eligible for enrollment to this study.

             12. Subject is currently receiving any chemotherapy, anticancer immunotherapy. Note:
             Subjects receiving corticosteroids will be eligible, but corticosteroids are expected
             to be tapered off as soon as possible from a clinical standpoint.

             13. Subject has clinically significant cardiovascular disease such as ventricular
             dysfunction, symptomatic coronary artery disease, 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 (NYHA) Functional Classification (Appendix D) at screening. Subjects with
             controlled, asymptomatic atrial fibrillation during screening can enroll on study.

             14. Subject has familial short QT syndrome. 15. Subject has a history of 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 that is likely to affect absorption.

             16. Subject has a known history of infection with HIV or any uncontrolled active
             significant infection (e.g., bacterial, viral or fungal).

             17. Subject has a known history of drug-specific hypersensitivity or anaphylaxis to
             acalabrutinib or isavuconazole (including active ingredient or excipient components).

             18. Subject has active bleeding or history of bleeding diathesis (e.g., hemophilia or
             von Willebrand disease).

             19. Subject has a history of uncontrolled AIHA (autoimmune hemolytic anemia) or ITP
             (idiopathic thrombocytopenic purpura).

             20. Subject has a history of significant cerebrovascular disease/event, including
             stroke or intracranial hemorrhage, within 6 months before the first dose of
             acalabrutinib.

             21. Subject had major surgical procedure within 28 days of first dose of
             acalabrutinib. 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 acalabrutinib.

             22. Subject must either have hepatitis B core antibody negative OR if a subject is
             hepatitis B core antibody positive they must have their hepatitis B viral load
             checked. These subjects will be excluded if their viral load is positive. Subject who
             are core antibody positive and viral load negative will be considered eligible, but
             must receive entecavir prophylaxis.

             23. Subjects who are hepatitis C antibody positive must have a negative polymerase
             chain reaction (PCR) result. Those who are hepatitis C PCR positive will be excluded.

             24. Subjects who are unable to swallow oral medications