Trial Outcomes & Findings for FCR and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia (CLL) (NCT NCT00448019)
NCT ID: NCT00448019
Last Updated: 2015-11-02
Results Overview
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
COMPLETED
PHASE2
64 participants
Baseline up to 5 years
2015-11-02
Participant Flow
Recruitment Period: February 23, 2007 to November 17, 2010. All recruitment done at The University of Texas MD Anderson Cancer Center.
Participant milestones
| Measure |
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.
|
|---|---|
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Overall Study
STARTED
|
64
|
|
Overall Study
COMPLETED
|
57
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Disease progression
|
1
|
|
Overall Study
Death
|
2
|
|
Overall Study
Insurance Issues
|
1
|
Baseline Characteristics
FCR and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
FCR + Bevacizumab
n=64 Participants
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.
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|---|---|
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Age, Continuous
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
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Region of Enrollment
United States
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64 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 5 yearsPopulation: Five participants of the 62 treated participants were not evaluable for response.
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
Outcome measures
| Measure |
FCR + Bevacizumab
n=57 Participants
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.
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|---|---|
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Progression Free Survival (PFS) Rate
|
13.5 Months
Interval 1.0 to 50.0
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SECONDARY outcome
Timeframe: Response assessed after three 4-week courses and after six courses, up to 24 weeksPopulation: Five participants of the 62 treated participants were not evaluable for response.
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).
Outcome measures
| Measure |
FCR + Bevacizumab
n=57 Participants
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.
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|---|---|
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Number of Participants With Complete or Partial Response to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Complete Response (CR)
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13 participants
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Number of Participants With Complete or Partial Response to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Partial Response (PR)
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24 participants
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Number of Participants With Complete or Partial Response to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Nodular Partial Response (NPR)
|
8 participants
|
SECONDARY outcome
Timeframe: Response assessed after three 4-week courses and after six courses, up to 24 weeksPopulation: Five participants of the 62 treated participants were not evaluable for response.
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).
Outcome measures
| Measure |
FCR + Bevacizumab
n=57 Participants
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.
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|---|---|
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Overall Response Rate (ORR) to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated CLL
|
79 percentage of participants
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Adverse Events
FCR + Bevacizumab
Serious adverse events
| Measure |
FCR + Bevacizumab
n=62 participants at risk
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.
|
|---|---|
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Blood and lymphatic system disorders
Anemia
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1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
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Blood and lymphatic system disorders
Gastrointestinal hemorrhage
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1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
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Gastrointestinal disorders
Dehydration
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Gastrointestinal disorders
Diarrhea
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Gastrointestinal disorders
Esophagitis
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Gastrointestinal disorders
Nausea
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
General disorders
Death
|
6.5%
4/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
General disorders
Fatigue
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
General disorders
Fever
|
3.2%
2/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
General disorders
Pain
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
General disorders
Tumor lysis Syndrome
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1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Infections and infestations
Herpes simplex II
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1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Infections and infestations
Infection
|
4.8%
3/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Infections and infestations
Neutropenic Fever
|
16.1%
10/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Infections and infestations
pneumonia
|
9.7%
6/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy
|
14.5%
9/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.2%
2/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
Other adverse events
| Measure |
FCR + Bevacizumab
n=62 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
66.1%
41/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
29.0%
18/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Infections and infestations
Infection
|
48.4%
30/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Gastrointestinal disorders
Nausea and vomiting
|
35.5%
22/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
General disorders
Fatigue
|
25.8%
16/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Blood and lymphatic system disorders
Anemia
|
14.5%
9/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Blood and lymphatic system disorders
Gastrointestinal Hemorrhage
|
3.2%
2/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.2%
2/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Eye disorders
Blurred vision
|
3.2%
2/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Nervous system disorders
Syncope
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
|
Cardiac disorders
Hypertension
|
1.6%
1/62 • Participants evaluated for adverse events at each study visit for study duration, up to six courses of 4 weeks. Overall collection period: May 2011 to September 2014.
|
Additional Information
MD Anderson Cancer Center Leukemia Department
The University of Texas (UT) MD Anderson Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60