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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00321724
First received: May 2, 2006
Last updated: January 14, 2013
Last verified: January 2013

May 2, 2006
January 14, 2013
May 2006
May 2007   (final data collection date for primary outcome measure)
Confirmed response defined to be an objective status of complete remission [CR], nodular partial remission [nPR], and partial remission [PR] [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Not Provided
Complete list of historical versions of study NCT00321724 on ClinicalTrials.gov Archive Site
  • Complete response rate estimated by the number of confirmed complete responses (CR) observed in the trial divided by the total number of evaluable patients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Exact binomial 95% confidence intervals for the true complete response rate will be calculated.
  • Overall survival [ Time Frame: From the date of registration to the date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.
  • Time to progression as estimated by Kaplan-Meier method [ Time Frame: From the date of registration to the date of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.
  • Duration of response [ Time Frame: From the date at which the patient's objective status is first noted to be a response to the date that progression or death is documented, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.
Not Provided
Not Provided
Not Provided
 
AZD2171 in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
A Phase II Trial of AZD2171 in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia Patients

This phase II trial is studying how well AZD2171 works in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia. AZD2171 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer cells

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B-cell Chronic Lymphocytic Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Drug: cediranib maleate
    Given orally
    Other Names:
    • AZD2171
    • Recentin
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (cediranib maleate)
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: cediranib maleate
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
Not Provided
May 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00321724
NCI-2012-01825, NCCTG-N048F, U10CA025224, CDR0000467560
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Neil Kay North Central Cancer Treatment Group
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP