A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Inclusion Criteria

Disease Related:

• Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.
• Age 65 yrs and older OR if less than 65 years, must have at least one of the following criteria:
• Cumulative Illness Rating Score (CIRS) >6
• Creatinine clearance estimated 10 percent within 6 months prior to screening.
• significant fatigue (inability to work or perform usual activities).
• fevers >100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence of infection.
• night sweats for more than 1 month prior to screening without evidence of infection.
• Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node >1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.

Laboratory

• Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization.
• Adequate hepatic and renal function
• Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Exclusion Criteria

• Any prior treatment of CLL or SLL
• Evidence of central nervous system (CNS) involvement with primary disease of CLL/SLL
• History of other malignancies, except:
• Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura
• Known or suspected history of Richter's transformation.
• Concurrent administration of >20mg/day of prednisone within 7 days of randomization unless indicated for prophylaxis or management of allergic reactions (eg, contrast)
• Known hypersensitivity to one or more study drugs
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Any uncontrolled active systemic infection or an infection requiring systemic treatment that was completed ≤ 7 days before randomization.
• Known bleeding disorders or hemophilia.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Major surgery within 4 weeks of randomization.
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• Concomitant use of warfarin or other vitamin K antagonists.
• Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
• Lactating or pregnant
• Unwilling or unable to participate in all required study evaluations and procedures.
• Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).