Ibrutinib and Obinutuzumab in Treating Patients with Previously Untreated Chronic Lymphocytic Leukemia

Inclusion Criteria

• Diagnosis of CLL: monoclonal B-cells co-expressing >= one B-cell marker (cluster of differentiation [CD]19, CD20, or CD23) and CD5 in peripheral blood or lymph node
• Indication for treatment as defined by the International Workshop in Chronic Lymphocytic Leukemia (IWCLL) Guidelines
• Massive (i.e. > 6 cm below the left costal margin) or progressive/symptomatic splenomegaly OR
• Massive lymph nodes or nodal clusters (i.e. > 10 cm in longest diameter), or progressive/symptomatic lymphadenopathy OR
• Presence of disease-related constitutional symptoms: * Weight loss >= 10% over the preceding 6 months * Significant fatigue (i.e., Eastern Cooperative Oncology Group [ECOG] performance status [PS] 2 or worse; inability to work or perform usual activities) * Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of infection * Night sweats for more than 1 month without evidence of infection
• Progressive lymphocytes with an increase of >= 50% over a 2-month period or an anticipated doubling time of less than 6 months OR
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
• No previous treatment for CLL
• Males and females 65 years of age and older; subjects < 65 years of age that meet any of the following criteria: * Subjects that refuse to be treated with chemotherapy based agents (this should be documented in the consent form) * Subjects that are not candidates for treatment with chemotherapy agents based on any of the following: ** ECOG performance status >= 2 ** Cumulative illness rating scale (CIRS score) >= 6 ** Creatinine clearance < 70 mL/min using the Cockcroft-Gault equation
• Hemoglobin >= 8 g/dL (may be post-transfusion)
• Platelet count >= 40 x 10^3/mm^3 (may be post-transfusion)
• Absolute neutrophil count >= 1.0 x 10^9 cells/L (growth factor use is allowed)
• Total bilirubin < 3 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN
• Creatinine clearance > 30 mL/min (calculated according to institutional standards or using Cockcroft–Gault formula; subjects with requirement of hemodialysis will be excluded)
• Anticipated survival of at least 6 months
• Effective contraception is required while receiving ibrutinib in combination with GA101 - obinutuzumab; for women of childbearing potential and men, effective contraception is required while receiving GA101 – obinutuzumab and for 365 days (12 months) after the last dose of the study drug
• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments
• Subjects must give written informed consent to participate in this trial

Exclusion Criteria

• Pregnant or nursing women
• Treatment with chemotherapy, monoclonal antibodies or biological agents (e.g. lenalidomide) other than the investigational agents during the time of participation in this trial
• Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, chronic obstructive pulmonary disease [COPD])
• Participation in any investigational drug study within 28 days prior to initiation of treatment within this protocol; (subject must have recovered from all acute effects of previously administered investigational agents)
• History of second malignancy, other than non-melanoma skin cancer or in situ carcinoma of the cervix or the breast, unless the tumor was successfully treated at least 2 years before trial entry and with no evidence of relapse or active cancer
• Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with human immunodeficiency virus (HIV), human T-cell leukemia virus 1 (HTLV-1) seropositive status
• Evidence of active acute or chronic hepatitis B (HBV); subjects with acute or chronic active HBV will be defined based on Centers for Disease Control and Prevention (CDC) guidelines; this will include subjects with positive serology for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc) associated with HBV-deoxyribonucleic acid (DNA) positive test by real time quantitative polymerase chain reaction (qPCR) assessment; subjects, who are anti-HBc positive and HBsAg negative or HBV-DNA test negative, may be enrolled in the study and should undergo regular monitoring of HBV viral load using HBV-DNA qPCR; those subjects may be referred to a hepatologist or gastroenterologist for appropriate monitoring and management including antiviral therapy
• Evidence of active hepatitis C (HCV); subjects with positive hepatitis C serology and positive HCV ribonucleic acid (RNA) test
• Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any the study’s endpoints
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to any of the study drugs
• Major surgery (within 4 weeks prior to the start of cycle 1), except for procedures that are performed for diagnostic purposes
• Men or women of childbearing potential who refuse to use an adequate measure of contraception (oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly) unless they have past medical history of surgical sterilization
• Vaccination with a live vaccine within 28 days of the initiation of treatment
• Concomitant use of warfarin or other vitamin K antagonists
• Requirement to receive treatment with a strong cytochrome P450 (CYP) 3A inhibitor