Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) or prolymphocytic leukemia (PLL) arising from CLL * No de novo PLL * Malignant B cells must co-express CD5 with CD19 or CD20 * Patients who lack CD23 expression on their leukemia cells may not have t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma * Must have documented lymphocytosis of \> 5,000/uL * Must require therapy based on any of the following criteria: * Massive or progressive splenomegaly and/or lymphadenopathy * Anemia (hemoglobin \< 11 g/dL) or thrombocytopenia (platelet count \< 100,000/uL) * Presence of weight loss \> 10% over the preceding 6-month period * NCI grade 2 or 3 fatigue * Fevers \> 100.5 F or night sweats for \> 2 weeks without evidence of infection * Progressive lymphocytosis with an increase of \> 50% over a 2-month period or an anticipated doubling time of less than 6 months * Must have received at least one prior therapy for B-CLL * No known brain metastases * ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% * Total bilirubin normal (unless due to Gilbert syndrome or compensated hemolysis) * Life expectancy \> 3 months * Creatinine normal * Fertile patients must use effective contraception * Not pregnant or nursing * Negative pregnancy test * Any number of prior therapies allowed * At least 1 year since prior fludarabine phosphate-rituximab combination therapy * No concurrent combination antiretroviral therapy for HIV-positive patients * No chemotherapy or radiotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C) * No other concurrent investigational agents * AST and ALT \< 2.5 times upper limit of normal * Recovered from all prior therapy Exclusion Criteria: * History of allergic reactions attributed to compounds of similar chemical or biologic composition to obatoclax mesylate or other agents used in study * Active Coombs' positive autoimmune hemolytic anemia * Chronic active hepatitis B patients if not on appropriate antiviral therapy (e.g., lamivudine, adefovir) * Other neurological disorders or dysfunction or a history of seizure disorder * Uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia including QTc \> 450 msec * Psychiatric illness/social situations that would limit compliance with study requirements