Chronic Lymphocytic LeukemiaPhase 2NCT00448019
FCR and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia (CLL)
A Phase 2 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Fludarabine, Cyclophosphamide and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Fludarabine, Cyclophosphamide, Rituximab and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia
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.
Read the 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.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Fludarabine, Cyclophosphamide, Rituximab, Bevacizumab
- Keywords
- Chronic Lymphocytic Leukemia, Fludarabine, Cyclophosphamide, Rituximab, Bevacizumab, CLL
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludara, Fludarabine Phosphate
25 mg/m^2 IV over 30 minutes daily for 3 days
CyclophosphamideDrug
Also called Cytoxan, Neosar
250 mg/m^2 IV over 30 minutes daily for 3 days
RituximabDrug
Also called Rituxan
375 mg/m^2 IV on Day 1 by prolonged infusion. All subsequent doses 500 mg/m^2 IV 30-minute infusion.
BevacizumabDrug
Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
10 mg/Kg IV on Day 3, course 1 over 30-90 minutes
| Study group | Role | What they receive |
|---|---|---|
| FCR + Bevacizumab | Experimental | 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. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline up to 5 years
Secondary outcomes (2)
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).
Measured: 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).
Measured: Response assessed after three 4-week courses and after six courses, up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2007 (estimated)
- Study startFeb 2007
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Susan O'Brien, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00448019
- Sponsor's protocol ID
- MDACC-2005-0992
- Other IDs
- NCI-2010-00591
- Status last verified
- Oct 2015
- First submitted
- 13 Mar 2007
- Last updated
- 2 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jain P, Lee HJ, Qiao W, Wierda W, Benjamini O, Burger J, Ferrajoli A, Estrov Z, Kantarjian H, Keating M, O'Brien S. FCR and bevacizumab treatment in patients with relapsed chronic lymphocytic leukemia. Cancer. 2014 Nov 15;120(22):3494-501. doi: 10.1002/cncr.28910. Epub 2014 Jul 15.
PubMed 25043749
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fludarabine, Cyclophosphamide, Rituximab and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00448019
- Acronym / sponsor ID
- MDACC-2005-0992
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- Chronic Lymphocytic Leukemia, Fludarabine, Cyclophosphamide, Rituximab, Bevacizumab, CLL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Feb 2007
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 15 Mar 2007 (estimated)
- Results
- Posted 2 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FCR + Bevacizumab | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Rituximab, Drug: BevacizumabFCR = 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineAlso: Fludara, Fludarabine Phosphate25 mg/m^2 IV over 30 minutes daily for 3 days | Drug | FCR + Bevacizumab |
| CyclophosphamideAlso: Cytoxan, Neosar250 mg/m^2 IV over 30 minutes daily for 3 days | Drug | FCR + Bevacizumab |
| RituximabAlso: Rituxan375 mg/m^2 IV on Day 1 by prolonged infusion. All subsequent doses 500 mg/m^2 IV 30-minute infusion. | Drug | FCR + Bevacizumab |
| BevacizumabAlso: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF10 mg/Kg IV on Day 3, course 1 over 30-90 minutes | Drug | FCR + Bevacizumab |
Primary outcome
Progression Free Survival (PFS) Rate
Time frame: Baseline up to 5 years
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
2 secondary outcomes
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25043749Jain P, Lee HJ, Qiao W, Wierda W, Benjamini O, Burger J, Ferrajoli A, Estrov Z, Kantarjian H, Keating M, O'Brien S. FCR and bevacizumab treatment in patients with relapsed chronic lymphocytic leukemia. Cancer. 2014 Nov 15;120(22):3494-501. doi: 10.1002/cncr.28910. Epub 2014 Jul 15.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan O'Brien, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) Rate (time frame: Baseline up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00448019, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2015.