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Fludarabine Phosphate, Rituximab, and Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia That Has Relapsed or Not Responded To Treatment

Phase 2
Withdrawn
Conditions
B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Interventions
Drug: fludarabine phosphate
Biological: rituximab
Biological: bevacizumab
Other: laboratory biomarker analysis
Other: flow cytometry
Genetic: polymerase chain reaction
Genetic: fluorescence in situ hybridization
Registration Number
NCT00845104
Lead Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab and bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fludarabine phosphate together with rituximab and bevacizumab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving fludarabine phosphate together with rituximab and bevacizumab works in treating patients with B-cell chronic lymphocytic leukemia that has relapsed or not responded to treatment.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate PFS at 2 years after FR plus Avastin (A) induction followed by Rituximab plus Avastin (RA) maintenance therapy for relapsed/refractory CLL patients.

SECONDARY OBJECTIVES:

I. To evaluate response rates after FR-A induction and RA maintenance therapy. II. To eliminate residual disease (documented by flow cytometry and/or PCR) in patients who have achieved a CR after FR-A.

III. To estimate the rate of conversion of PR to CR after FR-A. IV. To determine the safety and pharmacokinetics of FR-A and RA maintenance.

OUTLINE:

INDUCTION THERAPY: Patients receive fludarabine phosphate IV over 20-30 minutes once daily on days 1-5 and rituximab IV once daily on days 4 or 5. Treatment repeats every 35 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 8 of course 1, patients also receive bevacizumab IV over 30 minutes. Treatment repeats every 21 days for 9 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving complete response, partial response, or nodular partial response proceed to maintenance therapy.

MAINTENANCE THERAPY: Beginning 2 months after completion of induction treatment, patients receive rituximab IV every 3 months and bevacizumab IV over 30 minutes every 3 weeks. Treatment continues for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm IrituximabSee Detailed Description
Arm IbevacizumabSee Detailed Description
Arm Ilaboratory biomarker analysisSee Detailed Description
Arm Iflow cytometrySee Detailed Description
Arm Ipolymerase chain reactionSee Detailed Description
Arm Ifluorescence in situ hybridizationSee Detailed Description
Arm Ifludarabine phosphateSee Detailed Description
Primary Outcome Measures
NameTimeMethod
Progression-free survivalAt 2 years
Secondary Outcome Measures
NameTimeMethod
Response (complete, partial, or nodular partial response, progressive disease, stable disease, or minimal residual disease)At 2 years
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