Small Lymphocytic Lymphoma (SLL) Clinical Trials

• Diagnosis of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) as defined by the IWCLL including variation of flow cytometry, provided cytogenetic or mutational data are supportive of CLL/SLL diagnosis that requires therapy by one IWCLL criteria; and, must be previously untreated CLL/SLL.

• a. Note: Variation in flow cytometry is defined as patients who have atypical immunophenotyping for CLL (CD5 negative, CD23 negative or surface expression of CD79b that is bright) but clinically behave like CLL (leukocytosis, lymphadenopathy and splenomegaly) and have the FISH/Cytogenetics translocations (del 13q, trisomy 12, Del11q) or genomic features (XPO1, NOTCH1, SF3B1, FBXW7, MYD88, BIRC3, TRAF3, NFKBIE, SAMHD1, POT1, HIST1H1E, CHD2, ZMYM3, EGR2 and others) that are suggestive of CLL

• Men and Women ≥18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.

• Subjects must have adequate organ and marrow function as defined below:

‣ ANC ≥1,000/mcL, unless if neutropenia is due to extensive underlying CLL bone marrow disease then platelet threshold will be ANC ≥500/mcL unless WBC is \> to 50 x 109/L. If WBC is \> to 50 x 109/L there will be no lower threshold of ANC. Use of steroids for disease control is allowed.

⁃ Platelets ≥30,000/mcL unless thrombocytopenia is due to extensive underlying CLL bone marrow disease platelets threshold will be ≥ 10, 000/mcl. Use of steroids for disease control is allowed.

⁃ Total bilirubin ≤1.5 x ULN unless directly attributable to Gilbert's syndrome

⁃ AST and ALT ≤3 × ULN

⁃ Creatinine clearance (Cockcroft) ≥30 mL/min/1.73 m2 • CrCl by Cockcroft and Gault method: CrCl (mL/min) = (140 - age \[years\]) × weight (kg) × (F)a (72 × serum creatinine mg/dL a where F = 0.85 for females and F = 1 for males ≥ 30 mL/minute

• Female subjects who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib.

• Male subjects who are sexually active must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study.

• Men must agree to refrain from sperm donation during the study.

• Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing tablets without difficulty.

• 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 patient privacy regulations).