- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00448019
FCR and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia (CLL)
Fludarabine, Cyclophosphamide, Rituximab and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- University of Texas MD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of B-cell CLL
- Relapsed, fludarabine-sensitive (duration of response > 6 months as assessed by prior treating physician) or fludarabine-naive patients
- Rai Stage III or IV, or Rai Stage I or II if determined to have disease progression as evidenced by rapid doubling of peripheral lymphocyte count, progressive lymphadenopathy, progressive splenomegaly, or B symptoms.
- Prestudy WHO Performance Status </= 2.
- Signed, written Institutional Review Board (IRB)approved informed consent.
- Men and women of reproductive potential must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment.
- Acceptable liver function: Bilirubin </= 2.0 mg/dL (26 umol/L), AST (SGOT) and/or ALT (SGPT) </= 2 times upper limit of normal.
- Acceptable hematologic status: Platelet count >/= 50 x 10^9/L., absolute neutrophil count (ANC) >/= 1 x 10^9/L.
- Acceptable renal function: Serum creatinine </= 2.0 mg/dL
Exclusion Criteria:
- Cancer radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other investigational therapy within 4 weeks prior to Study Day 1.
- Known infection with HIV, hepatitis B, or hepatitis C
- Transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma, Richter's Syndrome, or prolymphocyte leukemia [PLL]).
- Patients with secondary malignancy requiring active treatment (except hormonal therapy).
- Active uncontrolled bacterial, viral, or fungal infections.
- New York Heart Association Class II-IV cardiac disease or myocardial infarction within the past 6 months prior to Study Day 1.
- Pregnant or currently breast-feeding.
- 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.
- Blood pressure of > 150/100 mmHg
- Unstable angina
- History of stroke within 6 months
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study.
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1.
- Urine protein:creatinine ratio >/= 1.0 at screening.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1.
- Serious, non-healing wound, ulcer, or bone fracture.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: FCR + Bevacizumab
FCR = Fludarabine 25 mg/m^2 intravenous (IV) , Cyclophosphamide 250 mg/m^2 IV daily for 3 days, Rituximab 375 mg/m^2 IV Day 1, followed by 500 mg/m^2 IV.
FCR daily for 3 days.
Bevacizumab 10 mg/Kg IV on Day 3, course 1.
|
25 mg/m^2 IV over 30 minutes daily for 3 days
Other Names:
250 mg/m^2 IV over 30 minutes daily for 3 days
Other Names:
375 mg/m^2 IV on Day 1 by prolonged infusion.
All subsequent doses 500 mg/m^2 IV 30-minute infusion.
Other Names:
10 mg/Kg IV on Day 3, course 1 over 30-90 minutes
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS) Rate
Time Frame: Baseline up to 5 years
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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
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Baseline up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Complete or Partial Response to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Time Frame: Response assessed after three 4-week courses and after six courses, up to 24 weeks
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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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Response assessed after three 4-week courses and after six courses, up to 24 weeks
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Overall Response Rate (ORR) to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated CLL
Time Frame: Response assessed after three 4-week courses and after six courses, up to 24 weeks
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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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Response assessed after three 4-week courses and after six courses, up to 24 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Susan O'Brien, MD, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Cyclophosphamide
- Bevacizumab
- Rituximab
- Fludarabine
- Fludarabine phosphate
Other Study ID Numbers
- MDACC-2005-0992
- NCI-2010-00591 (Registry Identifier: NCI CTRP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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