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