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Fludarabine (Fludara®) Plus Alemtuzumab (CAMPATH®, MabCampath®) vs Fludarabine Alone in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00086580
First received: July 6, 2004
Last updated: February 10, 2014
Last verified: February 2014
Results First Received: June 13, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: B-Cell Chronic Lymphocytic Leukemia
Interventions: Biological: FluCAM [Fludara + Campath]
Biological: fludarabine phosphate

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Treatment was from initiation of study drug(s) to 4 weeks after last administration of study drug. Follow-up was for those without disease progression and ended upon disease progression or primary endpoint analysis whichever came first. Observation included those with disease progression who were observed for alternative rx and overall survival.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Participant Flow for 3 periods

Period 1:   Treatment Period
    Combination Arm (FluCAM)     Fludarabine Alone  
STARTED     168     167  
Safety Population     164 [1]   165 [2]
COMPLETED     103 [3]   107 [4]
NOT COMPLETED     65     60  
Disease progression                 9                 8  
Unable to comply with protocol                 3                 1  
Withdrawal by Subject                 7                 8  
Physician Decision                 13                 7  
AE - not treatment related                 7                 7  
Toxicity - treatment related                 15                 15  
Anemia or thrombocytopenia                 1                 4  
Death                 5                 7  
Not specified                 5                 3  
[1] Four participants did not receive treatment
[2] Two participants did not receive treatment
[3] Finished 6 cycles of study drugs
[4] Finished 6 cycles of study drug

Period 2:   Follow-up Period
    Combination Arm (FluCAM)     Fludarabine Alone  
STARTED     141     137  
COMPLETED     37     18  
NOT COMPLETED     104     119  
Disease progression                 72                 99  
Unable to comply with protocol                 5                 0  
Withdrawal by Subject                 6                 6  
Physician Decision                 0                 1  
AE - not related                 1                 0  
Death                 13                 7  
Not specified                 7                 6  

Period 3:   Observation Period
    Combination Arm (FluCAM)     Fludarabine Alone  
STARTED     95     121  
COMPLETED     49     56  
NOT COMPLETED     46     65  
Unable to comply with protocol                 1                 1  
Withdrawal by Subject                 4                 2  
Death                 33                 55  
Not specified                 8                 7  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.
Total Total of all reporting groups

Baseline Measures
    Combination Arm (FluCAM)     Fludarabine Alone     Total  
Number of Participants  
[units: participants]
  168     167     335  
Age  
[units: years]
Mean ± Standard Deviation
  60.0  ± 9.25     60.8  ± 9.34     60.4  ± 9.29  
Gender  
[units: participants]
     
Female     59     59     118  
Male     109     108     217  
Race/Ethnicity, Customized  
[units: participants]
     
White     167     167     334  
Other     1     0     1  
Height  
[units: centimeters]
Mean ± Standard Deviation
  169.0  ± 8.88     169.4  ± 9.30     169.2  ± 9.08  
Body Surface Area (BSA)  
[units: meters^2]
Mean ± Standard Deviation
  1.87  ± 0.213     1.90  ± 0.218     1.88  ± 0.216  
Maximum Lymph Node Size [1]
[units: participants]
     
<5 centimeters     134     136     270  
>= 5 centimeters     34     31     65  
World Health Organization (WHO) Performance Status [2]
[units: participants]
     
WHO Performance Status = 0     81     72     153  
WHO Performance Status = 1     87     95     182  
Rai Stage Group [3]
[units: participants]
     
Rai Stage 0     2     2     4  
Rai Stage I - II     104     102     206  
Rai Stage III - IV     62     63     125  
Binet Stage [4]
[units: participants]
     
Binet Stage A     27     25     52  
Binet Stage B     89     89     178  
Binet Stage C     52     53     105  
Disease Status [5]
[units: participants]
     
Relapsed     101     101     202  
Refractory     67     66     133  
Summary of Prior Therapy by Type of Therapy [6]
[units: participants]
     
Fludarabine-containing therapy     25     26     51  
Non-fludarabine-containing therapy     143     141     284  
[1] The number of participants whose largest lymph node by physical exam assessment during a baseline visit fell within two categories: <5 cm and >=5 cm. If there is no enlarged lymph node, then size is classified as <5 cm.
[2] Per protocol, all participants had a WHO performance status of 0 or 1. A WHO performance status of 0 is defined as "patient is able to carry out all normal activity without restriction," and status of 1 is "patient is ambulatory and capable of all self-care but unable to carry out any work; up and about more than 50% of waking hours."
[3]

Rai staging is a way to categorize the disease progression of chronic lymphocytic leukemia (CLL); higher stages reflect increasing severity.

Rai Stage 0: Lymphocytosis only, Rai Stage I: Lymphocytosis with lymphadenopathy, Rai Stage II: Lymphocytosis with hepatomegaly or splenomegaly, Rai Stage III: Lymphocytosis with anemia, Rai Stage IV: Lymphocytosis with thrombocytopenia.

Per protocol, the 4 participants with Rai Stage 0 were eligible for the study because they had Binet Stage A.

[4]

Binet staging classifies CLL according to the number of lymphoid tissues involved, as well as the presence of low red blood cell count (anemia) or low number of blood platelets (thrombocytopenia).

Binet Stage A: fewer than three areas of enlarged lymphoid tissue. Enlarged lymph nodes of the neck, underarms, and groin, as well as the spleen, are each considered "one group," whether unilateral (one-sided) or bilateral (on both sides).

Binet Stage B: more than three areas of enlarged lymphoid tissue.

Binet Stage C: anemia plus thrombocytopenia (platelets <100 x 10^3/dL).

[5] Count of participants with refractory or relapsed disease at baseline (as reported by the investigator).
[6] Count of participants who had prior therapy categorized by type of therapy: fludarabine-containing therapy or non-fludarabine-containing therapy.



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment   [ Time Frame: Up to 6 years ]

Measure Type Primary
Measure Title Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment
Measure Description Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     167  
Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment  
[units: months]
Median ( 95% Confidence Interval )
  23.65  
  ( 19.180 to 28.360 )  
  16.48  
  ( 12.500 to 21.220 )  


Statistical Analysis 1 for Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] <0.001
Hazard Ratio (HR) [4] 0.610
95% Confidence Interval ( 0.467 to 0.795 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox proportional hazards model was stratified by Rai Stage Group
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)   [ Time Frame: Up to 9 months ]

Measure Type Secondary
Measure Title Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)
Measure Description Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.
Time Frame Up to 9 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     167  
Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)  
[units: participants]
   
Overall Response (CR+PR)     137     126  
Complete Response (CR)     21     7  
Partial Response (PR)     116     119  
Progressive Disease (PD)     6     9  
Stable Disease (SD)     12     21  
Not Evaluable (NE)     13     11  


Statistical Analysis 1 for Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.178
Mean Difference (Final Values) [4] 0.06
95% Confidence Interval ( -0.03 to 0.15 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison of Overall Response.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  CMH chi-square test for a difference in overall response rates between treatments stratified by Rai Stage Group.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value presented is adjusted for multiple tests using Hochberg procedure for 3 clinically important secondary endpoints: ORR, CR rates and OS.
[4] Other relevant estimation information:
  Difference and confidence interval (CI) calculated using the recommended method by Altman et al.

Statistical Analysis 2 for Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.018
Mean Difference (Final Values) [4] 0.08
95% Confidence Interval ( 0.02 to 0.15 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison of complete response (CR).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  CMH chi-square test for a difference in complete response rates between treatments stratified by Rai Stage Group.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value presented is adjusted for multiple tests using Hochberg procedure for 3 clinically important secondary endpoints: ORR, CR rates and OS.
[4] Other relevant estimation information:
  Difference and confidence interval (CI) calculated using the recommended method by Altman et al.



3.  Secondary:   Kaplan-Meier Estimates of Overall Survival Time   [ Time Frame: Up to 6 years ]

Measure Type Secondary
Measure Title Kaplan-Meier Estimates of Overall Survival Time
Measure Description Overall survival was defined as the time in days from the date of randomization to the date of death due to any cause plus 1 day for all participants. Results are stated in months.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     167  
Kaplan-Meier Estimates of Overall Survival Time  
[units: months]
Median ( 95% Confidence Interval )
  NA  
  ( NA to NA ) [1]
  52.93  
  ( 40.890 to NA ) [1]
[1] NA = values were not calculable since there were not enough events for the statistical estimation, ie, few participants died


Statistical Analysis 1 for Kaplan-Meier Estimates of Overall Survival Time
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.042
Cox Proportional Hazard [4] 0.648
95% Confidence Interval ( 0.449 to 0.937 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox proportional hazards model stratified by Rai Stage Group
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value presented is adjusted for multiple tests using Hochberg procedure for 3 clinically important secondary endpoints: ORR, CR rates and OS.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)   [ Time Frame: Up to 6 years ]

Measure Type Secondary
Measure Title Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)
Measure Description Time to disease progression was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease as determined by IRRP. Results are stated in months.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     167  
Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)  
[units: months]
Median ( 95% Confidence Interval )
  27.96  
  ( 22.340 to 31.910 )  
  18.68  
  ( 14.510 to 23.220 )  


Statistical Analysis 1 for Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] <0.001
Cox Proportional Hazard [4] 0.562
95% Confidence Interval ( 0.420 to 0.752 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox regression model stratified by Rai Stage Group.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)   [ Time Frame: Up to 6 years ]

Measure Type Secondary
Measure Title Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)
Measure Description Duration of response was analyzed for participants who achieved a complete response (CR) or partial response (PR) and was defined as the number of days from the first date of documented response to the date of progressive disease as determined by IRRP or death due to any cause. Results are stated in months.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set of participants who achieved a complete response or a partial response as determined by the IRRP.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  135     124  
Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)  
[units: months]
Median ( 95% Confidence Interval )
  25.10  
  ( 20.200 to 29.280 )  
  19.14  
  ( 14.140 to 21.910 )  

No statistical analysis provided for Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)



6.  Secondary:   Kaplan-Meier Estimates for Time to Alternative Therapy   [ Time Frame: Up to 6 years ]

Measure Type Secondary
Measure Title Kaplan-Meier Estimates for Time to Alternative Therapy
Measure Description Time to alternative therapy was defined as the number of days from the date of randomization to the date of first alternative therapy for chronic lymphocytic leukemia (CLL) or death resulting from any cause. Participants who had not received alternative therapy as of the data cutoff date were censored at the last follow-up visit assessment date plus 1 day. Results are stated in months.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     167  
Kaplan-Meier Estimates for Time to Alternative Therapy  
[units: months]
Median ( 95% Confidence Interval )
  25.43  
  ( 20.130 to 41.810 )  
  22.01  
  ( 20.130 to 27.830 )  


Statistical Analysis 1 for Kaplan-Meier Estimates for Time to Alternative Therapy
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.021
Cox Proportional Hazard [4] 0.718
95% Confidence Interval ( 0.543 to 0.951 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox proportional hazards model stratified by Rai Stage Group.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline   [ Time Frame: Day 0 (baseline) ]

Measure Type Secondary
Measure Title Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline
Measure Description EQ-5D™ is a trademark of the EuroQol Group. EQ-5D™ is a standardized instrument for use as a measure of health outcome. The questionnaire asks about health status along 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression, which are rated at three possible levels (no problems, some problems, extreme problems). The score ranges from best (+1) to worst (-0.59).
Time Frame Day 0 (baseline)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis dataset. Participants who provided valid answers on questionnaires are included.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     164  
Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline  
[units: units on a scale]
Mean ± Standard Deviation
  0.7959  ± 0.1868     0.7822  ± 0.2023  

No statistical analysis provided for Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline



8.  Secondary:   Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment   [ Time Frame: up to month 6 (end of treatment) ]

Measure Type Secondary
Measure Title Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment
Measure Description EQ-5D™ is a trademark of the EuroQol Group. EQ-5D™ is a standardized instrument for use as a measure of health outcome. The questionnaire asks about health status along 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression, which are rated at three possible levels (no problems, some problems, extreme problems). The score ranges from best (+1) to worst (-0.59).
Time Frame up to month 6 (end of treatment)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis dataset. Participants who provided valid answers on questionnaires are included.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  152     147  
Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment  
[units: units on a scale]
Mean ± Standard Deviation
  0.8049  ± 0.2752     0.7749  ± 0.2569  

No statistical analysis provided for Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment



9.  Secondary:   Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline   [ Time Frame: Day 0 (baseline) ]

Measure Type Secondary
Measure Title Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline
Measure Description The EuroQol Visual Analogue Scale (EQ-VAS) was also used to capture the self-rating of current health status using a visual "thermometer" with the end points of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom.
Time Frame Day 0 (baseline)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set. Participants who provided valid answers on questionnaires are included.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  167     161  
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline  
[units: units on a scale]
Mean ± Standard Deviation
  70.9  ± 18.01     70.2  ± 17.24  

No statistical analysis provided for Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline



10.  Secondary:   Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment   [ Time Frame: up to month 6 (end of treatment) ]

Measure Type Secondary
Measure Title Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment
Measure Description The EuroQol Visual Analogue Scale (EQ-VAS) was also used to capture the self-rating of current health status using a visual "thermometer" with the end points of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom.
Time Frame up to month 6 (end of treatment)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set. Participants who provided valid answers on questionnaires are included.

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  152     146  
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment  
[units: units on a scale]
Mean ± Standard Deviation
  77.1  ± 19.41     75.7  ± 17.98  

No statistical analysis provided for Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment



11.  Secondary:   Summary of Participants With Adverse Experiences (AEs)   [ Time Frame: Up to 6 years ]

Measure Type Secondary
Measure Title Summary of Participants With Adverse Experiences (AEs)
Measure Description Number of participants with adverse events (AEs). AEs were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were assessed for relatedness to study treatment (4 point scale from 'not related' to 'definitely related'). Categories reported include participant counts for treatment-emergent AEs, AEs for infections, serious AEs, AEs causing discontinuation of study drug(s), and deaths. Related AEs for the combination arm can be related to either fludarabine or alemtuzumab.
Time Frame Up to 6 years  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  164     165  
Summary of Participants With Adverse Experiences (AEs)  
[units: participants]
   
At least 1 treatment emergent AE     161     149  
At least 1 related treatment emergent AE     159     125  
At least 1 treatment-emergent infection     67     58  
At least 1 drug-related infection     44     30  
At least 1 serious AE     54     41  
At least 1 related serious AE     47     28  
Discontinuation of study drug due to AE     37     32  
Discontinuation of study drug due to related AE     32     24  
Deaths     10     12  
Patients who died due to a related AE     7     6  
Patients who died within 30 days of the last dose     4     7  

No statistical analysis provided for Summary of Participants With Adverse Experiences (AEs)



12.  Secondary:   Mean Systemic Clearance (CL) of Fludarabine   [ Time Frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion) ]

Measure Type Secondary
Measure Title Mean Systemic Clearance (CL) of Fludarabine
Measure Description Clearance of drug from plasma is affected by the absorption, distribution, metabolism and elimination of the drug. Mean systemic clearance of fludarabine is derived from plasma concentration versus time data.
Time Frame month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  17     12  
Mean Systemic Clearance (CL) of Fludarabine  
[units: liters/hour]
Mean ± Standard Deviation
  9.46  ± 4.31     9.54  ± 3.10  

No statistical analysis provided for Mean Systemic Clearance (CL) of Fludarabine



13.  Secondary:   Total Volume of Distribution (Vss) of Fludarabine   [ Time Frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion) ]

Measure Type Secondary
Measure Title Total Volume of Distribution (Vss) of Fludarabine
Measure Description The total volume of distribution (Vss) is the apparent volume in which fludarabine is distributed immediately after it has been injected intravenously and equilibrated between plasma and the surrounding tissues. Total volume of distribution (Vss) of fludarabine is derived from plasma concentration versus time data.
Time Frame month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  17     12  
Total Volume of Distribution (Vss) of Fludarabine  
[units: liters]
Mean ± Standard Deviation
  117  ± 64.3     172  ± 91.3  

No statistical analysis provided for Total Volume of Distribution (Vss) of Fludarabine



14.  Secondary:   Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)   [ Time Frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion) ]

Measure Type Secondary
Measure Title Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)
Measure Description AUC (0-tau) is the area under the plasma concentration curve for fludarabine over the dosage interval (tau).
Time Frame month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  17     12  
Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)  
[units: ng*h/mL]
Mean ± Standard Deviation
  8203  ± 6531     5669  ± 3888  

No statistical analysis provided for Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)



15.  Secondary:   Maximum Plasma Concentration (Cmax) of Fludarabine   [ Time Frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion) ]

Measure Type Secondary
Measure Title Maximum Plasma Concentration (Cmax) of Fludarabine
Measure Description Cmax is the maximum plasma concentration of fludarabine observed.
Time Frame month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic population

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  17     12  
Maximum Plasma Concentration (Cmax) of Fludarabine  
[units: ng/mL]
Mean ± Standard Deviation
  4084  ± 6089     1847  ± 1637  

No statistical analysis provided for Maximum Plasma Concentration (Cmax) of Fludarabine



16.  Secondary:   Participants With Minimal Residual Disease (MRD)   [ Time Frame: up to 9 months ]

Measure Type Secondary
Measure Title Participants With Minimal Residual Disease (MRD)
Measure Description MRD negativity in this report was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. MRD was assessed in participants with a clinical complete response (CR) or partial response (PR) without recovery of blood counts. MRD represents a very positive outcome.
Time Frame up to 9 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  168     167  
Participants With Minimal Residual Disease (MRD)  
[units: participants]
  6     0  


Statistical Analysis 1 for Participants With Minimal Residual Disease (MRD)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.014
Mean Difference (Final Values) [4] 0.04
95% Confidence Interval ( 0.01 to 0.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  CMH chi-square test for a difference in response rates between treatments stratified by Rai Stage Group.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



17.  Other Pre-specified:   Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage I-II   [ Time Frame: Up to 6 years ]

Measure Type Other Pre-specified
Measure Title Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage I-II
Measure Description Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months and include participants with Rai stage I or II.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set of participants with Rai stage I or II

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  104     102  
Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage I-II  
[units: months]
Median ( 95% Confidence Interval )
  23.75  
  ( 19.970 to 29.700 )  
  20.76  
  ( 14.700 to 24.340 )  


Statistical Analysis 1 for Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage I-II
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.102
Cox Proportional Hazard [4] 0.750
95% Confidence Interval ( 0.531 to 1.059 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



18.  Other Pre-specified:   Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage III-IV   [ Time Frame: Up to 6 years ]

Measure Type Other Pre-specified
Measure Title Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage III-IV
Measure Description Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months and include participants with Rai stage III or IV.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set of participants with Rai stage III or IV

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  62     63  
Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage III-IV  
[units: months]
Median ( 95% Confidence Interval )
  20.53  
  ( 14.310 to 31.910 )  
  11.51  
  ( 8.980 to 14.670 )  


Statistical Analysis 1 for Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) for Participants With Rai Stage III-IV
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] <0.001
Cox Proportional Hazard [4] 0.443
95% Confidence Interval ( 0.292 to 0.671 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



19.  Other Pre-specified:   Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage I-II   [ Time Frame: Up to 6 years ]

Measure Type Other Pre-specified
Measure Title Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage I-II
Measure Description Overall survival was defined as the time in days from the date of randomization to the date of death due to any cause plus 1 day for all participants. Results are stated in months and include participants with Rai Stage I or II.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set of participants with Rai Stage I or II

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  104     102  
Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage I-II  
[units: months]
Median ( 95% Confidence Interval )
  NA  
  ( 58.420 to NA ) [1]
  NA  
  ( 57.430 to NA ) [1]
[1] NA=values were not calculable since there were not enough events for the statistical estimation, ie, few participants died


Statistical Analysis 1 for Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage I-II
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.819
Cox Proportional Hazard [4] 1.066
95% Confidence Interval ( 0.619 to 1.836 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox proportional hazards model
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



20.  Other Pre-specified:   Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage III-IV   [ Time Frame: Up to 6 years ]

Measure Type Other Pre-specified
Measure Title Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage III-IV
Measure Description Overall survival was defined as the time in days from the date of randomization to the date of death due to any cause plus 1 day for all participants. Results are stated in months and include participants with Rai Stage III or IV.
Time Frame Up to 6 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set of participants with Rai Stage III or IV

Reporting Groups
  Description
Combination Arm (FluCAM) Participants received both fludarabine (Fludara) and alemtuzumab (Campath) intravenously. Initial escalation of alemtuzumab from 3 to 30 mg (escalation can take up to 14 days). Up to six cycles of fludarabine 30 mg/m^2 intravenous (IV) followed by alemtuzumab 30 mg IV on the first 3 days of each 28 day cycle.
Fludarabine Alone Participants received fludarabine monotherapy 25 mg/m^2 IV daily for the first 5 days of each 28 day cycle for up to 6 cycles.

Measured Values
    Combination Arm (FluCAM)     Fludarabine Alone  
Number of Participants Analyzed  
[units: participants]
  62     63  
Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage III-IV  
[units: months]
Median ( 95% Confidence Interval )
  NA  
  ( 32.140 to NA ) [1]
  23.52  
  ( 17.760 to 40.300 )  
[1] NA=values were not calculable since there were not enough events for the statistical estimation, ie, few participants died


Statistical Analysis 1 for Kaplan-Meier Estimates of Overall Survival Time for Participants With Rai Stage III-IV
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] <0.001
Cox Proportional Hazard [4] 0.416
95% Confidence Interval ( 0.250 to 0.690 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Cox proportional hazards model
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information