Acalabrutinib and Obinutuzumab for the Treatment of Chronic Lymphocytic Leukemia

Inclusion Criteria:

• Diagnosis CLL/small lymphocytic lymphoma (SLL) and be untreated

• Patients must have an indication for treatment by 2018 International Workshop onChronic Lymphocytic Leukemia (IWCLL) Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Patients of childbearing potential must be willing to practice highly effectivebirth control during treatment and for 2 days after the last dose of acalabrutinibor 18 months after the last dose of obinutuzumab, whichever is later

• A negative urine pregnancy test (within 7 days of day 1) is required for women withchildbearing potential

• Adequate renal and hepatic function as indicated by all of the following: Totalbilirubin =< 1.5 x institutional upper limit of normal (ULN) except for patientswith bilirubin elevation due to Gilbert's disease who will be allowed to participate

• An alanine transferase (ALT) =< 2.5 x ULN

• An estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by theCockcroft-Gault equation unless disease related

• Free of prior malignancies for 2 years with exception of patients diagnosed withbasal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of thecervix or breast who are eligible even if they are currently treated or have beentreated and/or diagnosed in the past 2 years prior to study enrollment. If patientshad another malignancy of indolent behavior in the past 2 years prior to studyenrollment that is expected to be cured with treatment they received such patientscan be enrolled, after consultation with the principal investigator

Exclusion Criteria:

• Pregnant or breast-feeding females

• Prior CLL/SLL treatment

• Known history of infection with human immunodeficiency virus (HIV) or anyuncontrolled active significant infection (eg, bacterial, viral or fungal)

• Signs of active hepatitis B or C. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have anegative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B PCR positive will be excluded. Subjects who arehepatitis C antibody positive will need to have a negative PCR result. Those who arehepatitis C PCR positive will be excluded

• Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmunethrombocytopenia (ITP)

• Patients with severe hematopoietic insufficiency as defined by an absoluteneutrophil count of less than 500/μL, unless disease-related, and/or a plateletcount of less than 30,000/μL at time of screening for this protocol.

• Clinically significant cardiovascular disease such as uncontrolled or symptomaticarrhythmias, congestive heart failure, or myocardial infarction within 6 months ofheart failure, or any class 3 or 4 cardiac disease as defined by the New York HeartAssociation Functional Classification. Subjects with controlled, asymptomatic atrialfibrillation can enroll. Patients with a history of paroxysmal atrial fibrillation (PAF) or deep vein thrombosis or pulmonary embolism (DVT/PE) can be included if theyhad no signs of PAF or DVT/PE in the last 6 months before enrolment. Patients withongoing atrial fibrillation (AFib) or ongoing PAF or DVT/PE should be excluded

• History of stroke or cerebral hemorrhage within 6 months

• Known history or evidence of bleeding diathesis or coagulopathy within 3 months

• Major surgical procedure, open biopsy, or significant traumatic injury within 28days

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 daysprior to day 1. Bone marrow aspiration and/or biopsy are allowed

• Serious, non-healing wound, ulcer, or bone fracture

• Treatment with warfarin (Coumadin) or any other vitamin K antagonist. Patients whorecently received warfarin must be off warfarin for at least 7 days prior to startof the study. Patients receiving novel oral anticoagulant (NOAC), also termed directoral anticoagulant (DOAC) are permitted to enroll. Patients who are currently on avitamin K antagonist must be switched to a non-vitamin K antagonist, such as aNOAC/DOAC

• Has difficulty with or is unable to swallow oral medication, or has significantgastrointestinal disease that would limit absorption of oral medication

• Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components)

• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer

• Prothrombin time (PT)/international normalized ratio (INR) or activated partialthromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x ULN

• Concurrent participation in another therapeutic clinical trial