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

This is an interventional treatment trial for B-cell Chronic Lymphocytic Leukemia Read More

Inclusion

• Relapse or refractory chronic Lymphocytic leukemia as defined by the WHO criteria and exhibit active disease requiring treatment as per the NCI working group in CLL
• Disease measurable defined by a combination of lymphocytosis >= 5,000/mm^3 in peripheral blood and lymphocytosis >= 30% in bone marrow
• Confirmed CD20 expression on malignant CLL cells
• ECOG performance status of 0-2
• Life expectancy of at least 6 months
• Documented negative serologic testing for human immunodeficiency virus (HIV), hepatitis B (unless serologically positive due to prior vaccination), and hepatitis C within the year prior to enrollment
• Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN)
• Total serum bilirubin < 2.5 x ULN
• Serum creatinine < 1.5 x ULN
• Hemoglobin > 8 g/dL
• Absolute neutrophil count (ANC) > 1,000 cells/mm^3
• Platelet count > 50,000/mm^3
• PT/INR and PTT < 1.5 x ULN
• Within 2 weeks prior to registration, patients must have had a urinalysis negative for protein or a 24-hour urine collection demonstrating < 500 mg protein
• If female and of child-bearing potential, have a negative serum pregnancy test within 14 days of enrollment
• If sexually active male or sexually active female of reproductive capability, has agreed to use a medically accepted form of contraception from time of enrollment to completion of all follow-up study visits
• Signed an institutional review board (IRB)-approved informed consent document for this protocol

Exclusion

• Patients must not require sustained support of hematopoietic cytokines or transfusion of blood products
• Presence of acute infection or other significant systemic illness
• Central nervous system involvement by malignancy, history of CVA, or seizure
• Previously received Bevacizumab
• Received transplant or Alemtuzumab within 3 months of enrollment
• Received an investigational agent, systemic corticosteroids, chemotherapy, immunotherapy, biologic therapy, antibody therapy (e.g., Rituximab) and/or radiation therapy within one month of enrollment
• Radiation to > 25% of bone marrow or any radiation therapy within 4 weeks prior to start of therapy
• Inability to comply with study and/or follow-up procedures
• Life expectancy of less than 6 months
• Fludarabine-refractory disease (no response of disease to >= 3 cycles of a fludarabine-based regimen or relapse within 6 months of fludarabine-based regimen)
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer (basal cell or squamous cell carcinoma), in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years unless approved by the PI
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1
• Known CNS disease, except for treated brain metastasis; Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria as demonstrated by a UPC ratio >= 1.0 at screening
• Known hypersensitivity to any component of bevacizumab
• Pregnancy (positive pregnancy test) or lactation; use of effective means of contraception (men and women) in subjects of childbearing potential