Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Inclusion Criteria:

   - PRE-REGISTRATION (STEP 0)

   - All patients are REQUIRED to be pre-registered to A041202 in order to submit
   peripheral blood to the Alliance Hematologic Malignancy Biorepository (HEME) for
   central Zap-70 methylation. This specimen submission is mandatory prior to
   registration as results will be used for stratification

   - REGISTRATION (STEP 1)

   - Patients must be diagnosed with CLL in accordance with International Workshop on
   Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following:

      - >= 5 x 10^9 B lymphocytes (5000/uL) in the peripheral blood

      - On morphologic review, the leukemic cells must be small mature lymphocytes, and
      prolymphocytes must not exceed 55% of the blood lymphocytes

      - CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell
      population, which express the B cell surface markers of CD19 and CD20, as well as
      the T-cell antigen CD5; patients with bright surface immunoglobulin expression or
      lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by
      interphase cytogenetics

   - Patients must be intermediate or high-risk Rai stage CLL

      - Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus
      enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly

      - High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without
      enlarged nodes and spleen plus disease-related anemia (hemoglobin < 11 g/dL) or
      thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to
      autoimmune hemolytic anemia or thrombocytopenia

   - Patients must meet criteria for treatment as defined by IWCLL 2008 guidelines which
   includes at least one of the following criteria:

      - Evidence of marrow failure as manifested by the development or worsening of
      anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or
      thrombocytopenia)

      - Massive (>= 6 cm below the costal margin), progressive or symptomatic
      splenomegaly

      - Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy

      - Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard
      therapy

      - Constitutional symptoms, which include any of the following:

         - Unintentional weight loss of 10% or more within 6 months

         - Significant fatigue

         - Fevers > 100.5 degrees F for 2 weeks or more without evidence of infection

         - Night sweats > 1 month without evidence of infection

   - Age >= 65 years

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

   - Patients with active hepatitis B defined by hepatitis B surface antigen positivity or
   core antibody positivity in the presence of hepatitis B DNA are not eligible for this
   study; patients with a positive hepatitis B core antibody but with negative hepatitis
   B DNA may participate, but must have hepatitis serologies and hepatitis B DNA
   monitored periodically by the treating physician

      - Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B
      serology; if patients receiving routine IVIG have core antibody or surface
      antigen positivity without evidence of active viremia (negative hepatitis B DNA)
      they may still participate in the study, but should have hepatitis serologies and
      hepatitis B DNA monitored periodically by the treating physician

   - Patients with class III or class IV heart failure by New York Heart Association, those
   with unstable angina, and those with uncontrolled arrhythmia are not eligible

   - Patients who have had a myocardial infarction, intracranial bleed, or stroke within
   the past 6 months are not eligible

   - Patients with known human immunodeficiency virus (HIV) are eligible if their CD4 count
   is >= 350 cells/mm^3 and if they are not taking prohibited CYP-interacting medications

   - Patients may not have had major surgery within 10 days of enrollment, or minor surgery
   within 7 days of enrollment; examples of minor surgery include dental surgery,
   insertion of a venous access device, skin biopsy, or aspiration of a joint; the
   decision about whether a surgery is major or minor can be made at the discretion of
   the treating physician

   - Absolute neutrophil count (ANC) >= 1,000/uL unless due to bone marrow involvement

   - Aspartate aminotransferase (AST) or alanine aminotransferase (AST) =< 2.5 x upper
   limits of normal except if due to disease infiltration of the liver

   - Bilirubin =< 1.5 x upper limits of normal (unless due to liver involvement, hemolysis,
   or Gilbert's disease)

   - Creatinine clearance >= 40 mL/min

      - To be calculated by modified Cockcroft-Gault formula

   - Platelet count (untransfused) >= 30,000/uL

Exclusion Criteria:

   - Prior treatment

      - Patients must not have had prior therapy for CLL (except palliative steroids or
      treatment of autoimmune complications of CLL with rituximab or steroids)

      - Treatment with rituximab and/or high dose corticosteroids for autoimmune
      complications of CLL must be complete at least 4 weeks prior to enrollment;
      palliative steroids must be at a dose not higher than 20 mg/day of prednisone or
      equivalent corticosteroid at the time of registration

   - Patients must not be receiving active systemic anticoagulation with heparin or
   warfarin; patients must be off warfarin therapy for at least 30 days prior to
   enrollment

   - Patients must not have any history of Richter's transformation or prolymphocytic
   leukemia (prolymphocytes in blood > 55%)

   - Patients must not require more than 20 mg prednisone or equivalent corticosteroid
   daily

   - Patients must not have uncontrolled active systemic infection requiring intravenous
   antibiotics

   - Patients must not have continued requirement for therapy with a strong cytochrome P450
   3A4/5 (CYP3A4/5) inhibitor or inducer

   - Patients must not have a known allergy to mannitol

   - Patients must not have prior significant hypersensitivity to rituximab (not including
   infusion reactions)