AZD2171 in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

Inclusion Criteria:

Histological confirmation of B-cell chronic lymphocytic leukemia (B-CLL)

Peripheral blood lymphocyte count > 5,000/mm³
Small to moderate peripheral blood lymphocytes with ≤ 55% prolymphocytes
Bone marrow aspirate with ≥ 30% lymphoid cells

Monoclonality of B lymphocytes by immunophenotyping, demonstrating all of the following:

B-cell markers with CD5 antigen in the absence of other pan-T-cell markers (CD3, CD2, etc.)
CD19 and/or CD20
Expression of CD23 on the CLL cells OR dim B-cell expression of kappa or lambda light chains
Disease must be refractory to or progressive after treatment with at least 1 course containing a purine nucleoside analog (e.g., fludarabine, cladribine, or pentostatin)
Life expectancy > 6 months
ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 50,000/mm³
Hemoglobin ≥ 8 g/dL

Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Patients with Gilbert's syndrome may have a bilirubin ≥ 1.5 times ULN
AST and ALT ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergies to compounds similar to AZD2171
QTc prolongation < 500 msec
No other significant ECG abnormality
No history of familial long QT syndrome
Proteinuria < 1+ by dipstick OR protein < 1 g/24 hr urine collection
No known HIV positivity

No New York Heart Association (NYHA) class III or IV disease

NYHA class II disease controlled with treatment and monitoring allowed

No other uncontrolled illness including, but not limited to, the following:

Hypertension
Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness or social situations that would limit compliance
See Disease Characteristics
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, anti-vascular endothelial growth factor (VEGF) treatment, or major surgery and recovered
More than 30 days since prior investigational agents
No concurrent drugs or biologics with proarrhythmic potential
No other concurrent investigational agents
No other concurrent anticancer therapy