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

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ClinicalTrials.gov Identifier: NCT00349349
Recruitment Status : Completed
First Posted : July 7, 2006
Results First Posted : November 29, 2011
Last Update Posted : June 4, 2014
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukaemia, Lymphocytic, Chronic
Intervention Drug: ofatumumab
Enrollment 223
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 95 112 16
Completed 42 50 10
Not Completed 53 62 6
Reason Not Completed
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Withdrawn due to Disease Progression             27             37             1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
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 95 112 16 223
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 95 participants 112 participants 16 participants 223 participants
63.2  (8.4) 64.4  (9.3) 64.5  (7.4) 63.9  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 112 participants 16 participants 223 participants
Female
24
  25.3%
31
  27.7%
5
  31.3%
60
  26.9%
Male
71
  74.7%
81
  72.3%
11
  68.8%
163
  73.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 95 participants 112 participants 16 participants 223 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
1.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Measure Type: Number
Unit of Measure: 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
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2000 mg Ofatumumab + DR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p value is testing the hypothesis that the response rate is equal to 15% versus the response rate is not equal to 15%.
Method Two-sided exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of responders
Estimated Value 0.49
Confidence Interval (2-Sided) 95.3%
0.39 to 0.60
Estimation Comments Two-sided 95.3% exact confidence intervals were calculated based on the binomial distribution.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2000 mg Ofatumumab + BFR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p value is testing the hypothesis that the response rate is equal to 15% versus the response rate is not equal to 15%.
Method Two-sided exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of responders
Estimated Value 0.43
Confidence Interval (2-Sided) 95.3%
0.33 to 0.53
Estimation Comments Two sided 95.3% exact confidence intervals were calculated based on the binomial distribution.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2000 mg Ofatumumab + Other
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The p value is testing the hypothesis that the response rate is equal to 15% versus the response rate is not equal to 15%.
Method Two-sided exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of responders
Estimated Value 0.63
Confidence Interval (2-Sided) 95.3%
0.35 to 0.85
Estimation Comments Two-sided 95.3% exact confidence intervals were calculated based on the binomial distribution.
2.Secondary Outcome
Title Duration of Response
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(3.7 to 7.2)
6.4
(4.6 to 7.0)
7.4
(2.8 to 12.4)
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (95% Confidence Interval)
Unit of Measure: months
4.6
(3.9 to 6.3)
5.5
(4.6 to 6.4)
8.9
(3.7 to 11.8)
4.Secondary Outcome
Title Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment
Hide 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])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (95% Confidence Interval)
Unit of Measure: months
8.5
(7.2 to 9.9)
8.2
(7.0 to 9.3)
12.1
(8.2 to 14.7)
5.Secondary Outcome
Title Overall Survival
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (95% Confidence Interval)
Unit of Measure: months
13.9
(9.8 to 18.6)
17.4
(15.0 to 24.5)
28.3
(19.0 to 29.2)
6.Secondary Outcome
Title Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (Full Range)
Unit of Measure: percent change in cell counts
-93
(-100 to 597)
-92
(-100 to 1384)
-95
(-100 to 640)
7.Secondary Outcome
Title Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (Full Range)
Unit of Measure: percent change in cell counts
-100
(-100 to 236)
-100
(-100 to -13)
-100
(-100 to -96)
8.Secondary Outcome
Title Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Median (Full Range)
Unit of Measure: percent change in tumor size
-81
(-100 to 100)
-80
(-100 to 335)
-82
(-100 to -6)
9.Secondary Outcome
Title Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.)
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 42 57 10
Measure Type: Number
Unit of Measure: participants
34 46 9
10.Secondary Outcome
Title Number of Participants With Complete Resolution of Lymphadenopathy
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.)
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 82 100 13
Measure Type: Number
Unit of Measure: participants
27 18 6
11.Secondary Outcome
Title Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.)
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 55 70 12
Measure Type: Number
Unit of Measure: participants
25 35 7
12.Secondary Outcome
Title Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 92 110 16
Measure Type: Number
Unit of Measure: 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
13.Secondary Outcome
Title Number of Participants With Improvement in Hemoglobin
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 49 62 8
Measure Type: Number
Unit of Measure: participants
18 20 5
14.Secondary Outcome
Title Number of Participants With Improvement in Thrombocytopenia (Thromb.)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 10 13 0
Measure Type: Number
Unit of Measure: participants
4 6
15.Secondary Outcome
Title Number of Participants With Complete Resolution of Hepatomegaly
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 21 28 7
Measure Type: Number
Unit of Measure: participants
17 19 4
16.Secondary Outcome
Title Number of Participants With Improvement in Neutropenia
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 30 25 3
Measure Type: Number
Unit of Measure: participants
20 17 1
17.Secondary Outcome
Title Number of Participants With Complete Resolution of Splenomegaly
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 43 63 10
Measure Type: Number
Unit of Measure: participants
28 38 5
18.Secondary Outcome
Title Number of Participants Who Experienced Any Adverse Event
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 95 112 16
Measure Type: Number
Unit of Measure: participants
90 107 16
19.Secondary Outcome
Title Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.
Arm/Group Title 2000 mg Ofatumumab + Total
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 215
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Milligrams per liter (mg/L)
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%)
20.Secondary Outcome
Title AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + Total
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 163
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Milligrams x hour per liter (mg.h/L)
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%)
21.Secondary Outcome
Title Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + Total
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 141
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
t1/2 at Dose 8, n=141
326
(0.56%)
t1/2 at Dose 12, n=81
277
(0.87%)
22.Secondary Outcome
Title Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + Total
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 163
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Milliliters per hour (mL/h)
CL at Dose 8, n=163
11.7
(0.48%)
CL at Dose 12, n=84
12.1
(1.23%)
23.Secondary Outcome
Title Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 2000 mg Ofatumumab + Total
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 133
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters (L)
Vss at Dose 8, n=133
4.84
(0.30%)
Vss at Dose 12, n=83
3.73
(0.30%)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   60/95 (63.16%)   59/112 (52.68%)   12/16 (75.00%) 
Blood and lymphatic system disorders       
Neutropenia  1  7/95 (7.37%)  3/112 (2.68%)  3/16 (18.75%) 
Febrile neutropenia  1  2/95 (2.11%)  3/112 (2.68%)  1/16 (6.25%) 
Hemolytic anaemia  1  0/95 (0.00%)  2/112 (1.79%)  0/16 (0.00%) 
Agranulocytosis  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Anemia  1  2/95 (2.11%)  1/112 (0.89%)  0/16 (0.00%) 
Anemia haemolytic autoimmune  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Lymphocytic infiltration  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Thrombocytopenia  1  4/95 (4.21%)  1/112 (0.89%)  0/16 (0.00%) 
Cardiac disorders       
Myocardial infarction  1  1/95 (1.05%)  2/112 (1.79%)  0/16 (0.00%) 
Myocardial ischaemia  1  0/95 (0.00%)  2/112 (1.79%)  0/16 (0.00%) 
Cardic failure  1  1/95 (1.05%)  1/112 (0.89%)  0/16 (0.00%) 
Myopericarditis  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Cardiac arrest  1  0/95 (0.00%)  2/112 (1.79%)  0/16 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Eye disorders       
Diplopia  1  1/95 (1.05%)  1/112 (0.89%)  0/16 (0.00%) 
Gastrointestinal disorders       
Small intestinal obstruction  1  1/95 (1.05%)  1/112 (0.89%)  0/16 (0.00%) 
Enteritis  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Ascites  1  1/95 (1.05%)  1/112 (0.89%)  0/16 (0.00%) 
Abdominal pain  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Constipation  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Diarrhea  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Gastrointestinal pain  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
General disorders       
Disease progression  1  4/95 (4.21%)  5/112 (4.46%)  1/16 (6.25%) 
Pyrexia  1  6/95 (6.32%)  4/112 (3.57%)  0/16 (0.00%) 
Hyperthermia  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Infusion related reaction  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Immune system disorders       
Cytokine release syndrome  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Hypersensitivity  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Contrast media allergy  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Immunodeficiency  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Infections and infestations       
Pneumonia  1  12/95 (12.63%)  12/112 (10.71%)  2/16 (12.50%) 
Sepsis  1  5/95 (5.26%)  6/112 (5.36%)  0/16 (0.00%) 
Bronchopneumonia  1  2/95 (2.11%)  1/112 (0.89%)  0/16 (0.00%) 
Herpes zoster  1  2/95 (2.11%)  1/112 (0.89%)  0/16 (0.00%) 
Neutropenic sepsis  1  4/95 (4.21%)  0/112 (0.00%)  1/16 (6.25%) 
Sinusitis  1  2/95 (2.11%)  2/112 (1.79%)  0/16 (0.00%) 
Urinary tract infection  1  2/95 (2.11%)  2/112 (1.79%)  0/16 (0.00%) 
Bronchitis  1  2/95 (2.11%)  0/112 (0.00%)  0/16 (0.00%) 
Septic shock  1  3/95 (3.16%)  0/112 (0.00%)  0/16 (0.00%) 
Lobar pneumonia  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Appendicitis  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Aspergilloma  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Cellulitis  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Enterocolitis infection  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Folliculitis  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Fusarium infection  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Gastroenteritis  1  1/95 (1.05%)  1/112 (0.89%)  0/16 (0.00%) 
Infection  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Injection site infection  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Lung infection  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Peritoneal infection  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Pneumocystis jiroveci pneumonia  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Pneumonia fungal  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Progessive multifocal  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Pseudomonas infection  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Upper respiratory tract infection  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Lower respiration infection  1  0/95 (0.00%)  2/112 (1.79%)  0/16 (0.00%) 
Ear infection  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Eczema infected  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Erysipelas  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Enterocolitis infections  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Escherichia sepsis  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Eye infection staphylococcal  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Influenza  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Nocardiosis  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Pseuromonas infection  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Respiratory tract infection  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Accidental overdose  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Postoperative fever  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Transfusion reaction  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Lower limb fracture  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Spinal compression fracture  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Investigations       
Blood lactate dehydrogenase increased  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Neutrophil count decreased  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Blood uric acid increased  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Metabolism and nutrition disorders       
Diabetes mellitus inadequate control  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Hypercalcaemia  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Diabetes  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Hypokalemia  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Arthralgia  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Bone pain  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  1/95 (1.05%)  1/112 (0.89%)  0/16 (0.00%) 
Chronic lympocytic leukaemia  1  1/95 (1.05%)  3/112 (2.68%)  0/16 (0.00%) 
Hodgkins disease  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Mantle cell lymphoma  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Chronic lymphocytic leukaemia transformation  1  2/95 (2.11%)  0/112 (0.00%)  0/16 (0.00%) 
Bladder cancer  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Bowen's disease  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Colon cancer  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Neoplasm  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Skin cancer  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Squamous cell carcinoma of the skin  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Tumor lysis syndrome  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Nervous system disorders       
Facial paresis  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Hemiparesis  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Ischaemic stroke  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Transient ischaemic attack  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Cerebral ischemia  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Epilepsy  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Psychiatric disorders       
Confusional state  1  2/95 (2.11%)  0/112 (0.00%)  0/16 (0.00%) 
Renal and urinary disorders       
Urinary retention  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Haemoptysis  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Hypoxia  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Pleural effusion  1  1/95 (1.05%)  0/112 (0.00%)  1/16 (6.25%) 
Pulmonary embolism  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Pulmonary edema  1  0/95 (0.00%)  2/112 (1.79%)  0/16 (0.00%) 
Acute repiratory failure  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Bronchospasm  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Dyspnea  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Lung disorder  1  0/95 (0.00%)  1/112 (0.89%)  0/16 (0.00%) 
Lung infiltration  1  0/95 (0.00%)  0/112 (0.00%)  1/16 (6.25%) 
Respiratory failure  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Skin and subcutaneous tissue disorders       
Pyroderma gangrenosum  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Rash  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  1/95 (1.05%)  2/112 (1.79%)  0/16 (0.00%) 
Haematoma  1  1/95 (1.05%)  0/112 (0.00%)  0/16 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
2000 mg Ofatumumab + DR 2000 mg Ofatumumab + BFR 2000 mg Ofatumumab + Other
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   90/95 (94.74%)   107/112 (95.54%)   16/16 (100.00%) 
Blood and lymphatic system disorders       
Anemia  1  17/95 (17.89%)  20/112 (17.86%)  2/16 (12.50%) 
Neutropenia  1  19/95 (20.00%)  13/112 (11.61%)  5/16 (31.25%) 
Gastrointestinal disorders       
Diarrhoea  1  16/95 (16.84%)  16/112 (14.29%)  5/16 (31.25%) 
Nausea  1  13/95 (13.68%)  15/112 (13.39%)  1/16 (6.25%) 
Vomiting  1  7/95 (7.37%)  7/112 (6.25%)  1/16 (6.25%) 
Abdominal pain  1  5/95 (5.26%)  7/112 (6.25%)  1/16 (6.25%) 
General disorders       
Fatigue  1  12/95 (12.63%)  22/112 (19.64%)  1/16 (6.25%) 
Pyrexia  1  22/95 (23.16%)  18/112 (16.07%)  7/16 (43.75%) 
Oedema peripheral  1  9/95 (9.47%)  14/112 (12.50%)  1/16 (6.25%) 
Chills  1  13/95 (13.68%)  13/112 (11.61%)  2/16 (12.50%) 
Infections and infestations       
Pneumonia  1  15/95 (15.79%)  15/112 (13.39%)  4/16 (25.00%) 
Bronchitis  1  14/95 (14.74%)  12/112 (10.71%)  0/16 (0.00%) 
Upper respiratory tract infection  1  4/95 (4.21%)  17/112 (15.18%)  2/16 (12.50%) 
Nasopharyngitis  1  10/95 (10.53%)  10/112 (8.93%)  1/16 (6.25%) 
Herpes zoster  1  6/95 (6.32%)  6/112 (5.36%)  0/16 (0.00%) 
Sinusitis  1  7/95 (7.37%)  7/112 (6.25%)  1/16 (6.25%) 
Urinary tract infection  1  4/95 (4.21%)  8/112 (7.14%)  1/16 (6.25%) 
Lower respiratory tract infections  1  5/95 (5.26%)  6/112 (5.36%)  3/16 (18.75%) 
Metabolism and nutrition disorders       
Decreased appetite  1  8/95 (8.42%)  4/112 (3.57%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  13/95 (13.68%)  7/112 (6.25%)  2/16 (12.50%) 
Muscle spasms  1  4/95 (4.21%)  7/112 (6.25%)  2/16 (12.50%) 
Nervous system disorders       
Headache  1  8/95 (8.42%)  5/112 (4.46%)  1/16 (6.25%) 
Parasthesia  1  5/95 (5.26%)  5/112 (4.46%)  2/16 (12.50%) 
Psychiatric disorders       
Insomnia  1  7/95 (7.37%)  7/112 (6.25%)  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  23/95 (24.21%)  24/112 (21.43%)  5/16 (31.25%) 
Dyspnoea  1  19/95 (20.00%)  12/112 (10.71%)  3/16 (18.75%) 
Skin and subcutaneous tissue disorders       
Rash  1  17/95 (17.89%)  8/112 (7.14%)  5/16 (31.25%) 
Urticaria  1  5/95 (5.26%)  9/112 (8.04%)  2/16 (12.50%) 
Hyperhidrosis  1  6/95 (6.32%)  8/112 (7.14%)  1/16 (6.25%) 
Vascular disorders       
Hypotension  1  7/95 (7.37%)  6/112 (5.36%)  1/16 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00349349     History of Changes
Other Study ID Numbers: 111773
Hx-CD20-406 ( Other Identifier: Genmab )
First Submitted: July 6, 2006
First Posted: July 7, 2006
Results First Submitted: October 20, 2011
Results First Posted: November 29, 2011
Last Update Posted: June 4, 2014