A Phase II Trial of AZD2171 in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia Patients
18 Years
N/A
Both
B-cell Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
Trial Information
A Phase II Trial of AZD2171 in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia Patients
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 between Rai stage at study entry and clinical response to AZD2171.
V. Perform preclinical testing of AZD2171 in the induction of B-CLL cell apoptosis/cell
death using pretreatment samples, and evaluate the ability to downregulate the
phosphorylation status of VEGFR-2 of B-CLL cells by comparing in vitro samples with and
without AZD2171.
VI. Study the differences in in vitro levels of B-CLL cell apoptosis/cell death and
alteration of VEGFR-2 phosphorylation using pretreatment samples with and without AZD2171
and how these differences correlate with clinical outcomes.
VII. Assess if the clinical responses are associated with changes in bone marrow
vascularity.
OUTLINE: This is a multicenter study.
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Patients undergo blood sampling and biopsies at baseline and periodically throughout study
for biomarker and correlative studies.
After completion of study therapy, patients are followed periodically for up to 5 years from
study entry.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Confirmed response defined to be an objective status of complete remission [CR], nodular partial remission [nPR], and partial remission [PR]
Outcome Description:
Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Outcome Time Frame:
Up to 5 years
Safety Issue:
No
Principal Investigator
Neil Kay
Investigator Role:
Principal Investigator
Investigator Affiliation:
North Central Cancer Treatment Group
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01825
NCT ID:
NCT00321724
Start Date:
May 2006
Completion Date:
Related Keywords:
- B-cell Chronic Lymphocytic Leukemia
- Refractory Chronic Lymphocytic Leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
Name | Location |
|---|---|
| North Central Cancer Treatment Group | Rochester, Minnesota 55905 |
