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