The goal of this clinical research study is to learn if the combination of fludarabine, cyclophosphamide, rituximab, and bevacizumab is effective in treating chronic lymphocytic leukemia in patients who have already been treated with chemotherapy. The safety of this treatment will also be studied.
During the study, you will have up to 6 "cycles" of treatment. A cycle is made up of treatment with the study drugs for 3-4 days and then about 3-1/2 weeks (25 days) of no treatment (about 4 weeks total). Treatment with the study drugs will be given for 4 days in a row on the first cycle, and 3 days in a row on Cycles 2-6. On Day 1 of each cycle, you will receive rituximab through a needle in a vein. On Cycle 1, since it is your first exposure to rituximab, it must be given slowly, so it may take 6-8 hours to complete. On the cycles after that, it can be given more rapidly, over 3-4 hours. Cyclophosphamide and fludarabine will be given separately through a needle in a vein on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2-6. Cyclophosphamide and fludarabine will each be given over 30 minutes. Bevacizumab will be given through a needle in a vein over 90 minutes on Day 3 of Cycle 1. If it is well tolerated, the next dose of Bevacizumab will be given over 60 minutes on Day 2 of Cycle 2. If the Cycle 2 dose is well tolerated, the next doses of Bevacizumab will be given over 30 minutes on Day 2 of Cycles 2-6. In addition to the study drugs, you may also be given fluids by vein to help flush the kidneys, to help prevent possible kidney damage. You may receive up to 6 cycles of treatment. Treatment will be given on an outpatient basis. The injections for each daily treatment visit should take less than 6 hours. Up to 66 patients will take part in the study. All will be enrolled at M.D. Anderson.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
64
25 mg/m\^2 IV over 30 minutes daily for 3 days
250 mg/m\^2 IV over 30 minutes daily for 3 days
375 mg/m\^2 IV on Day 1 by prolonged infusion. All subsequent doses 500 mg/m\^2 IV 30-minute infusion.
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Progression Free Survival (PFS) Rate
Progression free survival (PFS) was defined as the time from the start of treatment to progression, which included treatment failure, relapse, or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Baseline up to 5 years
Number of Participants With Complete or Partial Response to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Response criteria for Complete response (CR) - Nodes: None; Liver/Spleen Size: Not palpable; Symptoms: None; polymorphonuclear leukocytes (PMN): \>1,500/μl; Platelets \>100,000/μl; Hemoglobin (untransfused): \>11,0 g/dl; Lymphocytes: \<4,000/μl; Bone Marrow aspirate: \<30% lymphocytes; Biopsy: No lymphocyte infiltrate; and for Partial Response (PR), Nodes: \>/= 50% decrease; Liver/Spleen Size: \>/= 50% decrease; Symptoms: None; Platelets \>100,000/μl or \> 50% improvement from baseline; Hemoglobin (untransfused): \>11.0 g/dl or \>50% improvement from baseline; Lymphocytes: \>50% decrease; Biopsy: \<30% lymphocytes with residual disease on biopsy for nodular PR (NPR).
Time frame: Response assessed after three 4-week courses and after six courses, up to 24 weeks
Overall Response Rate (ORR) to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated CLL
ORR defined as CR and PR response where response criteria for Complete response (CR) - Nodes: None; Liver/Spleen Size: Not palpable; Symptoms: None; polymorphonuclear leukocytes (PMN): \>1,500/μl; Platelets \>100,000/μl; Hemoglobin (untransfused): \>11,0 g/dl; Lymphocytes: \<4,000/μl; Bone Marrow aspirate: \<30% lymphocytes; Biopsy: No lymphocyte infiltrate; and for Partial Response (PR), Nodes: \>/= 50% decrease; Liver/Spleen Size: \>/= 50% decrease; Symptoms: None; Platelets \>100,000/μl or \> 50% improvement from baseline; Hemoglobin (untransfused): \>11.0 g/dl or \>50% improvement from baseline; Lymphocytes: \>50% decrease; Biopsy: \<30% lymphocytes with residual disease on biopsy for nodular PR (NPR).
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10 mg/Kg IV on Day 3, course 1 over 30-90 minutes
Time frame: Response assessed after three 4-week courses and after six courses, up to 24 weeks