This is an open-label, multicenter, Phase I/II study of the safety of escalating doses of single-agent PRO131921 in patients with chronic lymphocytic leukemia (CLL) who have relapsed after or were refractory to treatment with a purine nucleoside analogue-containing regimen. The trial will enroll in two phases: a Phase I dose-escalation portion and a Phase II expanded treatment cohort, with enrollment of additional patients in order to expand safety experience and collect preliminary anti-leukemia activity data.

Inclusion Criteria:

• Documented history of histologically confirmed B-cell CLL
• Relapsed or refractory CLL with history of prior treatment with purine nucleoside analogue-containing regimen
• Eligible for treatment of their CLL based on criteria adapted from the National Cancer Institute-Working Group (NCI-WG) Response Criteria for CLL
• For patients of reproductive potential (males and females), use of a reliable means of contraception
• For females of childbearing potential, a negative serum pregnancy test

Exclusion Criteria:

• Prior use of anti-CD20 monoclonal antibody therapy (other than rituximab)
• Prior use of any non-CD20 targeted monoclonal antibody therapy within 6 months of enrollment
• Current or recent CLL treatment
• History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
• Evidence of acute/active autoimmune hemolytic anemia or other autoimmune complications of CLL
• Use of hematopoietic growth factors or RBC and/or platelet transfusions
• Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders
• Evidence of myelodysplasia or myelodysplastic changes on bone marrow examination
• History of cancer other than CLL)
• Known active bacterial, viral, fungal, mycobacterial, or other infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics or oral antibiotics
• A major episode of infection requiring hospitalization or treatment with IV antimicrobials within 4 weeks of screening or oral antimicrobials within 2 weeks of screening
• Positive hepatitis B or C serology
• Positive human immunodeficiency virus (HIV) serology
• Active cytomegalovirus (CMV) disease by antigen or polymerase chain reaction testing
• Pregnancy or lactation
• CNS leukemia
• Recent major surgery, other than diagnostic surgery