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

Launched by NATIONAL CANCER INSTITUTE (NCI) · May 2, 2006

Keywords

ClinConnect Summary

OBJECTIVES:

I. Evaluate the response rate in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL) treated with AZD2171.

II. Evaluate the toxicity of AZD2171 in patients with relapsed or refractory B-CLL.

III. Evaluate the complete response rate, progression-free and overall survival distributions, and duration of response in patients with relapsed or refractory B-CLL treated with AZD2171.

IV. Assess vascular endothelial growth factor receptor-2 (VEGFR-2) protein and phosphorylation levels in B-CLL cells using pretreatment samples and evaluate the association ...

Gender

ALL

Eligibility criteria

• 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