HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00349349
First received: July 6, 2006
Last updated: May 29, 2014
Last verified: June 2013
Results First Received: October 20, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukaemia, Lymphocytic, Chronic
Intervention: Drug: ofatumumab

  Participant Flow
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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
No text entered.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The independent endpoint review committee (IRC) classified these participants as double refractory (DR), defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Participant Flow:   Overall Study
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
STARTED     95     112     16  
COMPLETED     42     50     10  
NOT COMPLETED     53     62     6  
Adverse Event                 5                 6                 2  
Withdrawal by Subject                 5                 2                 1  
Withdrawn due to Disease Progression                 27                 37                 1  
Death                 13                 10                 1  
Other Treatment Selected                 2                 0                 0  
Participant Reduced General Condition                 0                 1                 0  
Physician Decision                 1                 2                 1  
No Response                 0                 3                 0  
New Malignancy (Bladder Cancer)                 0                 1                 0  



  Baseline Characteristics
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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
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.
Total Total of all reporting groups

Baseline Measures
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other     Total  
Number of Participants  
[units: participants]
  95     112     16     223  
Age  
[units: Years]
Mean ± Standard Deviation
  63.2  ± 8.4     64.4  ± 9.3     64.5  ± 7.4     63.9  ± 8.8  
Gender  
[units: Participants]
       
Female     24     31     5     60  
Male     71     81     11     163  
Race/Ethnicity, Customized  
[units: participants]
       
Asian     1     0     1     2  
Black or African American     2     1     0     3  
Hispanic or Latino     1     0     0     1  
White     88     111     15     214  
Arab     1     0     0     1  
Yemenite     1     0     0     1  
Middle Eastern     1     0     0     1  



  Outcome Measures
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1.  Primary:   Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 24 ]

Measure Type Primary
Measure Title Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
Measure Description Par. with complete remission (CR), nodular partial remission (nPR), and partial remission (PR) were classified as responders, while those with stable disease (SD) and progressive disease (PD) were classified as non-responders. Per the NCIWG guideline (1996): CR; no lymphadenopathy/hepatomegaly/splenomegaly/constitutional symptoms, normal hematology, bone marrow sample as normocellular for age, <30% lymphocytes (LC), no lymphoid nodule; PR: a >=50% decrease in LC/lymphadenopathy; nPR: persistent nodules in bone marrow; PD: new lesion or increase by >=50% from baseline; SD: no CR, PR, or PD.
Time Frame Start of treatment (Week 0 of Visit 2) until Week 24  
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 (FAS): all participants who had been exposed to study drug irrespective of their compliance to the planned course of treatment. Participants not evaluable (NE) were due to patient withdraw, refusal, non-trial drug related AEs, and death

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines  
[units: participants]
     
Responders with CR     0     2     0  
Responders with nPR     0     0     1  
Responders with PR     47     46     9  
Non-responders with SD     33     52     4  
Non-responders with PD     5     9     1  
NE     10     3     1  


Statistical Analysis 1 for Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
Groups [1] 2000 mg Ofatumumab + DR
Method [2] Two-sided exact binomial test
P Value [3] <0.0001
percentage of responders [4] 0.49
95.3% Confidence Interval ( 0.39 to 0.60 )
[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:
  The p value is testing the hypothesis that the response rate is equal to 15% versus the response rate is not equal to 15%.
[4] Other relevant estimation information:
  Two-sided 95.3% exact confidence intervals were calculated based on the binomial distribution.

Statistical Analysis 2 for Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
Groups [1] 2000 mg Ofatumumab + BFR
Method [2] Two-sided exact binomial test
P Value [3] <0.0001
percentage of responders [4] 0.43
95.3% Confidence Interval ( 0.33 to 0.53 )
[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:
  The p value is testing the hypothesis that the response rate is equal to 15% versus the response rate is not equal to 15%.
[4] Other relevant estimation information:
  Two sided 95.3% exact confidence intervals were calculated based on the binomial distribution.

Statistical Analysis 3 for Number of Participants (Par.) Classified as Responders and Non-responders for Objective Response as Assessed by an Independent Endpoint Review Committee (IRC) in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
Groups [1] 2000 mg Ofatumumab + Other
Method [2] Two-sided exact binomial test
P Value [3] <0.001
percentage of responders [4] 0.63
95.3% Confidence Interval ( 0.35 to 0.85 )
[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:
  The p value is testing the hypothesis that the response rate is equal to 15% versus the response rate is not equal to 15%.
[4] Other relevant estimation information:
  Two-sided 95.3% exact confidence intervals were calculated based on the binomial distribution.



2.  Secondary:   Duration of Response   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 24 ]

Measure Type Secondary
Measure Title Duration of Response
Measure Description Duration of response is defined as the time from the initial response (first visit at which response is observed) to progression or death. If the participant had progression between scheduled visits, no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment, and experienced death or progression after two or more missed visits in a row the endpoint was censored.
Time Frame Start of treatment (Week 0 of Visit 2) until Week 24  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Duration of Response  
[units: months]
Median ( 95% Confidence Interval )
  5.5  
  ( 3.7 to 7.2 )  
  6.4  
  ( 4.6 to 7.0 )  
  7.4  
  ( 2.8 to 12.4 )  

No statistical analysis provided for Duration of Response



3.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Start of treatment (Week 0 of Visit 2) until Week 24 ]

Measure Type Secondary
Measure Title Progression-Free Survival (PFS)
Measure Description PFS is defined as the time from randomization until progression/death. Per the IRC, if the participant had progression between scheduled visits, died before the first assessment, or died between adequate visits, the endpoint was considered progressed. If there was no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity/other reason, new anti-cancer treatment, and death/progression after 2 or more missed visits in a row, the endpoint was censored. Clinical progression is not considered as progression endpoint.
Time Frame Start of treatment (Week 0 of Visit 2) until Week 24  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Progression-Free Survival (PFS)  
[units: months]
Median ( 95% Confidence Interval )
  4.6  
  ( 3.9 to 6.3 )  
  5.5  
  ( 4.6 to 6.4 )  
  8.9  
  ( 3.7 to 11.8 )  

No statistical analysis provided for Progression-Free Survival (PFS)



4.  Secondary:   Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment   [ Time Frame: Time from randomization (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (assessed for a median of 8.7 weeks currently [or up to 13.3 months]) ]

Measure Type Secondary
Measure Title Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment
Measure Description Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).
Time Frame Time from randomization (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (assessed for a median of 8.7 weeks currently [or up to 13.3 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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment  
[units: months]
Median ( 95% Confidence Interval )
  8.5  
  ( 7.2 to 9.9 )  
  8.2  
  ( 7.0 to 9.3 )  
  12.1  
  ( 8.2 to 14.7 )  

No statistical analysis provided for Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment



5.  Secondary:   Overall Survival   [ Time Frame: Start of randomization (Week 0 of Visit 2) until death (up to a median of 17.1 weeks) ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description OS is defined as the time from allocation to death. OS will also be subgrouped for responders and non-responders.
Time Frame Start of randomization (Week 0 of Visit 2) until death (up to a median of 17.1 weeks)  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Overall Survival  
[units: months]
Median ( 95% Confidence Interval )
  13.9  
  ( 9.8 to 18.6 )  
  17.4  
  ( 15.0 to 24.5 )  
  28.3  
  ( 19.0 to 29.2 )  

No statistical analysis provided for Overall Survival



6.  Secondary:   Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts   [ Time Frame: Baseline (Visit 2) until Week 7 (Visit 9) ]

Measure Type Secondary
Measure Title Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts
Measure Description The peripheral blood for each participant was collected and analyzed for CD5+CD19+ cell counts. CD is “cluster of differentiation,” is a cell surface marker for immunophenotyping, and, in this case, is a surrogate for B cell malignancy (indicates malignant B cells). Percent change from Visit 2 (Week 0, Baseline) = (value at Week 7 minus value at Week 0 divided by value at Week 0) x 100.
Time Frame Baseline (Visit 2) until Week 7 (Visit 9)  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts  
[units: percent change in cell counts]
Median ( Full Range )
  -93  
  ( -100 to 597 )  
  -92  
  ( -100 to 1384 )  
  -95  
  ( -100 to 640 )  

No statistical analysis provided for Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts



7.  Secondary:   Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts   [ Time Frame: Baseline (Visit 2) until Week 7 (Visit 9) ]

Measure Type Secondary
Measure Title Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts
Measure Description The peripheral blood for each participant was collected and analyzed for CD5+CD20+ cell counts. CD is “cluster of differentiation,” is a cell surface marker for immunophenotyping, and, in this case, is a surrogate for B cell malignancy (indicates malignant B cells). Percent change from Visit 2 (Week 0, Baseline) = (value at Week 7 minus value at Week 0 divided by value at Week 0) x 100.
Time Frame Baseline (Visit 2) until Week 7 (Visit 9)  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts  
[units: percent change in cell counts]
Median ( Full Range )
  -100  
  ( -100 to 236 )  
  -100  
  ( -100 to -13 )  
  -100  
  ( -100 to -96 )  

No statistical analysis provided for Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts



8.  Secondary:   Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)   [ Time Frame: Baseline (Visit 2) until Week 24 (Visit 14) ]

Measure Type Secondary
Measure Title Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)
Measure Description Tumor size and change in tumor size will be measured by the absolute value of and the percent change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24 (Visit 14). Percent change from Visit 2 (Baseline, Week 0) = (value at Week 24 minus value at Week 0 divided by value at Week 0) x 100.
Time Frame Baseline (Visit 2) until Week 24 (Visit 14)  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)  
[units: percent change in tumor size]
Median ( Full Range )
  -81  
  ( -100 to 100 )  
  -80  
  ( -100 to 335 )  
  -82  
  ( -100 to -6 )  

No statistical analysis provided for Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)



9.  Secondary:   Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24   [ Time Frame: Baseline (Visit 2) and Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24
Measure Description Participants with complete resolution of constitutional symptoms were those in whom no constitutional symptoms, such as night sweats, weight loss, and fever or extreme fatigue, were observed.
Time Frame Baseline (Visit 2) and Week 24  
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.
FAS. Data were provided for the number of participants with constitutional symptoms at baseline attending each visit. Participants withdrawn during the study were not analyzed. (Participants without baseline constitutional symptoms did not experience new constitutional symptoms during the trial period.)

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  42     57     10  
Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24  
[units: participants]
  34     46     9  

No statistical analysis provided for Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24



10.  Secondary:   Number of Participants With Complete Resolution of Lymphadenopathy   [ Time Frame: Baseline (Visit 2) to end of study (up to Week 24) ]

Measure Type Secondary
Measure Title Number of Participants With Complete Resolution of Lymphadenopathy
Measure Description Participants with complete resolution of lymphadenopathy (disease involving the lymph nodes) were defined as those in whom all observed lymph nodes were of normal size (all nodes <1 centimeters) as determined by physical examination assessed by the investigator. All palpable lymph node sizes were recorded.
Time Frame Baseline (Visit 2) to end of study (up to Week 24)  
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.
FAS. Data were provided for the number of participants with lymphadenopathy at baseline attending each visit. Participants withdrawn during the study were not analyzed. (Participants without baseline lymphadenopathy remained free of lymphadenopathy during the trial.)

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  82     100     13  
Number of Participants With Complete Resolution of Lymphadenopathy  
[units: participants]
  27     18     6  

No statistical analysis provided for Number of Participants With Complete Resolution of Lymphadenopathy



11.  Secondary:   Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24   [ Time Frame: Baseline (Visit 2) and Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24
Measure Description ECOG performance status is a measure of the participant’s ability to carry out activities of daily living on 6-point scale (0=fully active, 1=restricted in physically activity, ambulatory, 2=ambulatory [>50% of waking hours], 3=capable of only limited self care, 4=completely disabled, 5=Dead). Improvement in ECOG performance status is defined as a decrease from baseline by at least one score on the ECOG scale.
Time Frame Baseline (Visit 2) and Week 24  
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.
FAS. Data were provided for participants (par.) with an ECOG score >0 at baseline attending each visit. Par. withdrawn from the study were not analyzed. (55 par. had an ECOG performance status of 0 at baseline and therefore did not have the opportunity to improve. No par. with an ECOG score of 0 at baseline worsened during the trial.)

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  55     70     12  
Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24  
[units: participants]
  25     35     7  

No statistical analysis provided for Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24



12.  Secondary:   Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening   [ Time Frame: Screening (Visit 1, <=14 days prior to Visit 2) ]

Measure Type Secondary
Measure Title Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening
Measure Description The number of participants (par.) who were positive, negative, or had missing data for the following prognostic factors indicative of altered responsiveness to treatment and/or survival was measured: 17p-, 11q-, +12q, 6q-, 13q-. Par. were assessed by FISH for these chromosomal abnormalities known tobe prognostic for time to treatment and survival when detected at diagnosis. Par. were categorized by the chromosomal abnormality detected: 17 p deletion, 11q deletion (but not 17 p deletion), 12 q trisomy (but not 17 p or 111q deletion), 13q deletion only, and no chromosomal abnormalities found.
Time Frame Screening (Visit 1, <=14 days prior to Visit 2)  
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.
FAS. Par. were categorized hierarchically (by severity of abnormality): par. with a 17 p deletion (D); par. with an 11q D, but not a 17 p D; par. with 12q trisomy, but not a 17p or 11q D; par. with no aberrations found; par. with a 13q D as the sole aberration; and par. with 6q D (and not any of the above categories). Some par. had missing data.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  92     110     16  
Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening  
[units: participants]
     
FISH 17p-, negative     64     89     14  
FISH 17p-, positive     27     19     1  
FISH 17p-, missing     4     4     1  
FISH 11q-, negative     56     69     11  
FISH 11q-, positive     36     41     5  
FISH 11q-, missing     3     2     0  
FISH +12q, negative     76     91     11  
FISH +12q, positive     15     19     5  
FISH +12q, missing     4     2     0  
FISH 6q-, negative     89     101     15  
FISH 6q-, positive     2     9     0  
FISH 6q-, missing     4     2     1  
FISH 13q-, negative     46     53     9  
FISH 13q-, positive     45     57     7  
FISH 13q-, missing     4     2     0  

No statistical analysis provided for Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening



13.  Secondary:   Number of Participants With Improvement in Hemoglobin   [ Time Frame: Baseline (Visit 2) to Week 28 ]

Measure Type Secondary
Measure Title Number of Participants With Improvement in Hemoglobin
Measure Description The number of participants (par.) who had improvement in hemoglobin levels >=11 grams (g)/deciliter (dl) (6.8 millimoles/liter) or 50% improvement over baseline was measured.
Time Frame Baseline (Visit 2) to Week 28  
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.
FAS. Par. were excluded from analysis if they received treatment of red blood cells (RBCs), received transfusions or a RBC growth factor (erythropoietin), died, withdrew from the trial, or began next CLL treatment. Only those par. remaining in the study at Week 28 were analyzed. No par. in the “Other” treatment arm met the criteria for analysis.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  49     62     8  
Number of Participants With Improvement in Hemoglobin  
[units: participants]
  18     20     5  

No statistical analysis provided for Number of Participants With Improvement in Hemoglobin



14.  Secondary:   Number of Participants With Improvement in Thrombocytopenia (Thromb.)   [ Time Frame: Baseline (Visit 2) to Week 28 ]

Measure Type Secondary
Measure Title Number of Participants With Improvement in Thrombocytopenia (Thromb.)
Measure Description Improvement in thromb. is defined as a decrease from Visit 2 by >=1 National Cancer Institute Common Terminology Criteria (NCI CTC) grade. Thromb. is defined as low platelet counts resulting from refractory CLL, damage from prior treatment, advanced age, or reduced bone marrow function and can be considered as an adverse condition. Adverse events (AEs) such as thromb. in a cancer indication are graded on a scale determined by the NCI called the NCI CTC: lowest, grade 1; highest, grade 5 (death). Changes in this grading can assess improvements or declines in the severity of the AE.
Time Frame Baseline (Visit 2) to Week 28  
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.
FAS. Only those participants remaining in the study at Week 28 were analyzed. No par. in the “Other” treatment arm met the criteria for analysis.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  10     13     0  
Number of Participants With Improvement in Thrombocytopenia (Thromb.)  
[units: participants]
  4     6      

No statistical analysis provided for Number of Participants With Improvement in Thrombocytopenia (Thromb.)



15.  Secondary:   Number of Participants With Complete Resolution of Hepatomegaly   [ Time Frame: Baseline (Visit 2) until Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Complete Resolution of Hepatomegaly
Measure Description Participants with complete resolution of enlarged liver (hepatomegaly) were defined as those with an enlarged palpable liver at baseline followed by the absence of hepatomegaly post- baseline (i.e., the liver was of normal size). Liver size was assessed by physical examination and documented as “centimeters” under the costal margin with relative changes in spleen size in 1 dimension calculated based on palpated numeric measurements (as per the 1996 NCIWG guidelines).
Time Frame Baseline (Visit 2) until Week 24  
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.
FAS. Data were provided for the number of participants with hepatomegaly from baseline attending each visit. Participants withdrawn during the study were not analyzed. Only participants with baseline hepatomegaly and a post-baseline assessment are included.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  21     28     7  
Number of Participants With Complete Resolution of Hepatomegaly  
[units: participants]
  17     19     4  

No statistical analysis provided for Number of Participants With Complete Resolution of Hepatomegaly



16.  Secondary:   Number of Participants With Improvement in Neutropenia   [ Time Frame: Baseline (Visit 2) to Week 28 ]

Measure Type Secondary
Measure Title Number of Participants With Improvement in Neutropenia
Measure Description Low levels of neutrophils (neutropenia) may increase the risk of developing serious infections and may be considered an adverse condition and evaluated on the NCI CTC with a grade. Improvement in neutropenia is defined as a decrease from Visit 2 (baseline) by at least one NCI CTC grade. Improvement is defined as a decrease from Visit 2 by at least one NCI CTC grade.
Time Frame Baseline (Visit 2) to Week 28  
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.
FAS. Only those par. remaining in the study at Week 28 were analyzed. No par. in the “Other” treatment arm met the criteria for analysis.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  30     25     3  
Number of Participants With Improvement in Neutropenia  
[units: participants]
  20     17     1  

No statistical analysis provided for Number of Participants With Improvement in Neutropenia



17.  Secondary:   Number of Participants With Complete Resolution of Splenomegaly   [ Time Frame: Baseline (Visit 2) until Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Complete Resolution of Splenomegaly
Measure Description Participants with complete resolution of enlarged spleen (splenomegaly) were defined as those with an enlarged palpable spleen at baseline followed by the absence of splenomegaly post-baseline (i.e., the spleen was of normal size). Spleen size was assessed by physical examination and documented as “centimeters” under the costal margin with relative changes in spleen size in 1 dimension calculated based on palpated numeric measurements (as per the 1996 NCIWG guidelines).
Time Frame Baseline (Visit 2) until Week 24  
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.
FAS. Data were provided for the number of participants with splenomegaly at baseline attending each visit. Participants withdrawn during the study were not analyzed. Only participants with baseline splenomegaly and a post-baseline assessment are included.

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  43     63     10  
Number of Participants With Complete Resolution of Splenomegaly  
[units: participants]
  28     38     5  

No statistical analysis provided for Number of Participants With Complete Resolution of Splenomegaly



18.  Secondary:   Number of Participants Who Experienced Any Adverse Event   [ Time Frame: From first infusion (Visit 2/Week 0) to Visit 21 (Month 24 of follow-up [up to Month 48]) or time of withdrawal (treatment and follow-up) ]

Measure Type Secondary
Measure Title Number of Participants Who Experienced Any Adverse Event
Measure Description An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.
Time Frame From first infusion (Visit 2/Week 0) to Visit 21 (Month 24 of follow-up [up to Month 48]) or time of withdrawal (treatment and follow-up)  
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.
FAS

Reporting Groups
  Description
2000 mg Ofatumumab + DR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as DR, defined as participants who were enrolled in the study and were refractory to both fludarabine and alemtuzumab.
2000 mg Ofatumumab + BFR Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as BFR, defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy.
2000 mg Ofatumumab + Other Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. The IRC classified these participants as "other,"defined as participants who were enrolled in the study but did not meet criteria for DR or BFR.

Measured Values
    2000 mg Ofatumumab + DR     2000 mg Ofatumumab + BFR     2000 mg Ofatumumab + Other  
Number of Participants Analyzed  
[units: participants]
  95     112     16  
Number of Participants Who Experienced Any Adverse Event  
[units: participants]
  90     107     16  

No statistical analysis provided for Number of Participants Who Experienced Any Adverse Event



19.  Secondary:   Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 2 (Week 0), Visit 9 (Week 7), and Visit 14 (Week 24) ]

Measure Type Secondary
Measure Title Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)
Measure Description Cmax is defined as the maximum concentration of drug in serum samples. Ctrough is defined as the trough serum concentration (measured concentration at the end of a dosing interval [taken directly before the next administration]). No drug was present before the first infusion; therefore, there are no Ctrough results for Dose 1
Time Frame Visit 2 (Week 0), Visit 9 (Week 7), and Visit 14 (Week 24)  
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.
FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Reporting Groups
  Description
2000 mg Ofatumumab + Total Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. Data from all three groups of participants (DR, BFR, and Other) have been combined.

Measured Values
    2000 mg Ofatumumab + Total  
Number of Participants Analyzed  
[units: participants]
  215  
Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)  
[units: Milligrams per liter (mg/L)]
Geometric Mean ( Geometric Coefficient of Variation )
 
Cmax at Dose 1, n=215     61.4  
  ( 0.73% )  
Ctrough at Dose 8, n=192     549  
  ( 2.34% )  
Cmax at Dose 8, n=193     1391  
  ( 0.46% )  
Ctrough at Dose 12, n=106     32.1  
  ( 58.8% )  
Cmax at Dose 12, n=106     827  
  ( 0.41% )  

No statistical analysis provided for Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)



20.  Secondary:   AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit 14 (Week 24) ]

Measure Type Secondary
Measure Title AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)
Measure Description AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-inf) is AUC from the start of infusion extrapolated to infinity. AUC(0-tau) is AUC from the start of infusion over the dosing interval.
Time Frame Visit 9 (Week 7) and Visit 14 (Week 24)  
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.
FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

Reporting Groups
  Description
2000 mg Ofatumumab + Total Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. Data from all three groups of participants (DR, BFR, and Other) have been combined

Measured Values
    2000 mg Ofatumumab + Total  
Number of Participants Analyzed  
[units: participants]
  163  
AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)  
[units: Milligrams x hour per liter (mg.h/L)]
Geometric Mean ( Geometric Coefficient of Variation )
 
AUC(0-inf) at Dose 8, n=133     463418  
  ( 0.94% )  
AUC(0-inf) at Dose 12, n=83     203536  
  ( 1.64% )  
AUC(0-tau) at Dose 8, n=163     171286  
  ( 0.48% )  
AUC(0-tau) at Dose 12, n=84     165617  
  ( 1.23% )  

No statistical analysis provided for AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)



21.  Secondary:   Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit14 (Week 24) ]

Measure Type Secondary
Measure Title Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)
Measure Description Half-life ( t1/2) is defined as the terminal half-life and is the time required for the amount of drug in the body to decrease by half.
Time Frame Visit 9 (Week 7) and Visit14 (Week 24)  
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.
FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

Reporting Groups
  Description
2000 mg Ofatumumab + Total Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. Data from all three groups of participants (DR, BFR, and Other) have been combined.

Measured Values
    2000 mg Ofatumumab + Total  
Number of Participants Analyzed  
[units: participants]
  141  
Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)  
[units: hours]
Geometric Mean ( Geometric Coefficient of Variation )
 
t1/2 at Dose 8, n=141     326  
  ( 0.56% )  
t1/2 at Dose 12, n=81     277  
  ( 0.87% )  

No statistical analysis provided for Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)



22.  Secondary:   Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit 14 (Week 24) ]

Measure Type Secondary
Measure Title Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)
Measure Description CL is the clearance of drug from serum, which is defined as the volume of serum from which the drug is cleared per unit time.
Time Frame Visit 9 (Week 7) and Visit 14 (Week 24)  
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.
FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

Reporting Groups
  Description
2000 mg Ofatumumab + Total Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. Data from all three groups of participants (DR, BFR, and Other) have been combined.

Measured Values
    2000 mg Ofatumumab + Total  
Number of Participants Analyzed  
[units: participants]
  163  
Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)  
[units: Milliliters per hour (mL/h)]
Geometric Mean ( Geometric Coefficient of Variation )
 
CL at Dose 8, n=163     11.7  
  ( 0.48% )  
CL at Dose 12, n=84     12.1  
  ( 1.23% )  

No statistical analysis provided for Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)



23.  Secondary:   Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)   [ Time Frame: Visit 9 (Week 7) and Visit 14 (Week 24) ]

Measure Type Secondary
Measure Title Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)
Measure Description Vss is defined as the volume of distribution at steady state of ofatumumab.
Time Frame Visit 9 (Week 7) and Visit 14 (Week 24)  
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.
FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

Reporting Groups
  Description
2000 mg Ofatumumab + Total Ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions and then four monthly infusions of 2000 mg for a duration of 24 weeks. Data from all three groups of participants (DR, BFR, and Other) have been combined.

Measured Values
    2000 mg Ofatumumab + Total  
Number of Participants Analyzed  
[units: participants]
  133  
Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)  
[units: Liters (L)]
Geometric Mean ( Geometric Coefficient of Variation )
 
Vss at Dose 8, n=133     4.84  
  ( 0.30% )  
Vss at Dose 12, n=83     3.73  
  ( 0.30% )  

No statistical analysis provided for Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)




  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
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