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:
• •1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.
• •2. 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 \<70 mL/min using Cockcroft-Gault equation.
• •* Del 17p by fluorescence in situ hybridization (FISH) or TP53 mutation by polymerase chain reaction (PCR) or Next Generation Sequencing
• •3. Active disease meeting at least 1 of the following IWCLL criteria for requiring treatment:
• •* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and thrombocytopenia
• •* Massive, progressive, or symptomatic splenomegaly
• •* Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic lymphadenopathy.
• •* Progressive lymphocytosis with an increase of more than 50 percent over a 2-month period or a lymphocyte doubling time (LDT) of \<6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of \<30,000/µL, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
• •* Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy.
• •* Autoimmune hemolytic anemia is defined by at least one marker of hemolysis (indirect bilirubin above the upper limit of normal (ULN) not due to liver disease, increased lactate dehydrogenase (above ULN) without alternative etiology, or increased absolute reticulocytosis (above ULN) or bone marrow erythropoiesis in the absence of bleeding AND at least one marker direct or indirect autoimmune mechanism (positive direct antiglobulin for immunoglobulin G \[IgG\] or C3d, cold agglutinins).
• •* Immune thrombocytopenia is defined by platelets ≤100,000/µL and increased megakaryocytes on the bone marrow exam.
• •* Constitutional symptoms, defined as one or more of the following disease-related symptoms or signs, documented in the patient's record prior to randomization:
• •* unintentional weight loss \>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.
• •4. 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
• •5. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization.
• •6. Adequate hepatic and renal function
• •7. Men and women ≥ 18 years of age.
• •8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.