HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT00349349
Collaborator
(none)
223
1
72
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether HuMax-CD20 (ofatumumab) is effective in the treatment of patients failing both fludarabine and alemtuzumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
223 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single-arm, International, Multi-center Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20 Antibody, in Patients With B-cell Chronic Lymphocytic Leukemia Who Have Failed Fludarabine and Alemtuzumab
Study Start Date
:
Jun 1, 2006
Actual Primary Completion Date
:
May 1, 2008
Actual Study Completion Date
:
Jun 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ofatumumab Anti-CD20 antibody therapy |
Drug: ofatumumab
Intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- 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 [Start of treatment (Week 0 of Visit 2) until Week 24]
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.
Secondary Outcome Measures
- Duration of Response [Start of treatment (Week 0 of Visit 2) until Week 24]
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.
- Progression-Free Survival (PFS) [Start of treatment (Week 0 of Visit 2) until Week 24]
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 to Next Chronic Lymphocytic Leukemia (CLL) Treatment [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])]
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).
- Overall Survival [Start of randomization (Week 0 of Visit 2) until death (up to a median of 17.1 weeks)]
OS is defined as the time from allocation to death. OS will also be subgrouped for responders and non-responders.
- Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts [Baseline (Visit 2) until Week 7 (Visit 9)]
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.
- Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts [Baseline (Visit 2) until Week 7 (Visit 9)]
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.
- Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14) [Baseline (Visit 2) until Week 24 (Visit 14)]
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.
- Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24 [Baseline (Visit 2) and Week 24]
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.
- Number of Participants With Complete Resolution of Lymphadenopathy [Baseline (Visit 2) to end of study (up to Week 24)]
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.
- Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24 [Baseline (Visit 2) and Week 24]
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.
- Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening [Screening (Visit 1, <=14 days prior to Visit 2)]
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.
- Number of Participants With Improvement in Hemoglobin [Baseline (Visit 2) to Week 28]
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.
- Number of Participants With Improvement in Thrombocytopenia (Thromb.) [Baseline (Visit 2) to Week 28]
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.
- Number of Participants With Complete Resolution of Hepatomegaly [Baseline (Visit 2) until Week 24]
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).
- Number of Participants With Improvement in Neutropenia [Baseline (Visit 2) to Week 28]
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.
- Number of Participants With Complete Resolution of Splenomegaly [Baseline (Visit 2) until Week 24]
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).
- Number of Participants Who Experienced Any Adverse Event [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)]
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.
- Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24) [Visit 2 (Week 0), Visit 9 (Week 7), and Visit 14 (Week 24)]
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
- AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24) [Visit 9 (Week 7) and Visit 14 (Week 24)]
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.
- Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24) [Visit 9 (Week 7) and Visit14 (Week 24)]
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.
- Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24) [Visit 9 (Week 7) and Visit 14 (Week 24)]
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.
- Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24) [Visit 9 (Week 7) and Visit 14 (Week 24)]
Vss is defined as the volume of distribution at steady state of ofatumumab.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Tumor cell phenotype consistent with B-CLL
-
Patients with active B-CLL and with an indication for treatment
-
Failing at least one fludarabine-containing treatment regimen
-
Failing at least one alemtuzumab-containing treatment regimen
-
ECOG Performance Status of 0, 1, or 2
-
Life expectancy of at least 4 months
Exclusion Criteria:
-
Previous treatment with alemtuzumab within 6 weeks prior to Visit 2
-
Previous autologous stem cell transplantation within 6 months prior to Visit 2
-
Allogeneic stem cell transplantation
-
Radioimmunotherapy
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00349349
Other Study ID Numbers:
- 111773
- Hx-CD20-406
First Posted:
Jul 7, 2006
Last Update Posted:
Jun 4, 2014
Last Verified:
Jun 1, 2013
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other | Total |
|---|---|---|---|---|
| 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 Participants | 95 | 112 | 16 | 223 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
63.2
(8.4)
|
64.4
(9.3)
|
64.5
(7.4)
|
63.9
(8.8)
|
| Sex: Female, Male (Count of 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 (participants) [Number] | ||||
| Asian |
1
1.1%
|
0
0%
|
1
6.3%
|
2
0.9%
|
| Black or African American |
2
2.1%
|
1
0.9%
|
0
0%
|
3
1.3%
|
| Hispanic or Latino |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| White |
88
92.6%
|
111
99.1%
|
15
93.8%
|
214
96%
|
| Arab |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Yemenite |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Middle Eastern |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
Outcome Measures
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Responders with CR |
0
0%
|
2
1.8%
|
0
0%
|
| Responders with nPR |
0
0%
|
0
0%
|
1
6.3%
|
| Responders with PR |
47
49.5%
|
46
41.1%
|
9
56.3%
|
| Non-responders with SD |
33
34.7%
|
52
46.4%
|
4
25%
|
| Non-responders with PD |
5
5.3%
|
9
8%
|
1
6.3%
|
| NE |
10
10.5%
|
3
2.7%
|
1
6.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 2000 mg Ofatumumab + DR |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | percentage of responders |
| Estimated Value | 0.49 | |
| Confidence Interval |
(2-Sided) 95.3% 0.39 to 0.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Two-sided 95.3% exact confidence intervals were calculated based on the binomial distribution. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2000 mg Ofatumumab + BFR |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | percentage of responders |
| Estimated Value | 0.43 | |
| Confidence Interval |
(2-Sided) 95.3% 0.33 to 0.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Two sided 95.3% exact confidence intervals were calculated based on the binomial distribution. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 2000 mg Ofatumumab + Other |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | percentage of responders |
| Estimated Value | 0.63 | |
| Confidence Interval |
(2-Sided) 95.3% 0.35 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Two-sided 95.3% exact confidence intervals were calculated based on the binomial distribution. | |
| Title | Duration of Response |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (95% Confidence Interval) [months] |
5.5
|
6.4
|
7.4
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (95% Confidence Interval) [months] |
4.6
|
5.5
|
8.9
|
| Title | Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment |
|---|---|
| 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]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (95% Confidence Interval) [months] |
8.5
|
8.2
|
12.1
|
| Title | Overall Survival |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (95% Confidence Interval) [months] |
13.9
|
17.4
|
28.3
|
| Title | Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (Full Range) [percent change in cell counts] |
-93
|
-92
|
-95
|
| Title | Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (Full Range) [percent change in cell counts] |
-100
|
-100
|
-100
|
| Title | Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14) |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Median (Full Range) [percent change in tumor size] |
-81
|
-80
|
-82
|
| Title | Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 42 | 57 | 10 |
| Number [participants] |
34
35.8%
|
46
41.1%
|
9
56.3%
|
| Title | Number of Participants With Complete Resolution of Lymphadenopathy |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 82 | 100 | 13 |
| Number [participants] |
27
28.4%
|
18
16.1%
|
6
37.5%
|
| Title | Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 55 | 70 | 12 |
| Number [participants] |
25
26.3%
|
35
31.3%
|
7
43.8%
|
| Title | Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 92 | 110 | 16 |
| FISH 17p-, negative |
64
67.4%
|
89
79.5%
|
14
87.5%
|
| FISH 17p-, positive |
27
28.4%
|
19
17%
|
1
6.3%
|
| FISH 17p-, missing |
4
4.2%
|
4
3.6%
|
1
6.3%
|
| FISH 11q-, negative |
56
58.9%
|
69
61.6%
|
11
68.8%
|
| FISH 11q-, positive |
36
37.9%
|
41
36.6%
|
5
31.3%
|
| FISH 11q-, missing |
3
3.2%
|
2
1.8%
|
0
0%
|
| FISH +12q, negative |
76
80%
|
91
81.3%
|
11
68.8%
|
| FISH +12q, positive |
15
15.8%
|
19
17%
|
5
31.3%
|
| FISH +12q, missing |
4
4.2%
|
2
1.8%
|
0
0%
|
| FISH 6q-, negative |
89
93.7%
|
101
90.2%
|
15
93.8%
|
| FISH 6q-, positive |
2
2.1%
|
9
8%
|
0
0%
|
| FISH 6q-, missing |
4
4.2%
|
2
1.8%
|
1
6.3%
|
| FISH 13q-, negative |
46
48.4%
|
53
47.3%
|
9
56.3%
|
| FISH 13q-, positive |
45
47.4%
|
57
50.9%
|
7
43.8%
|
| FISH 13q-, missing |
4
4.2%
|
2
1.8%
|
0
0%
|
| Title | Number of Participants With Improvement in Hemoglobin |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 49 | 62 | 8 |
| Number [participants] |
18
18.9%
|
20
17.9%
|
5
31.3%
|
| Title | Number of Participants With Improvement in Thrombocytopenia (Thromb.) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 10 | 13 | 0 |
| Number [participants] |
4
4.2%
|
6
5.4%
|
| Title | Number of Participants With Complete Resolution of Hepatomegaly |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 21 | 28 | 7 |
| Number [participants] |
17
17.9%
|
19
17%
|
4
25%
|
| Title | Number of Participants With Improvement in Neutropenia |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 30 | 25 | 3 |
| Number [participants] |
20
21.1%
|
17
15.2%
|
1
6.3%
|
| Title | Number of Participants With Complete Resolution of Splenomegaly |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 43 | 63 | 10 |
| Number [participants] |
28
29.5%
|
38
33.9%
|
5
31.3%
|
| Title | Number of Participants Who Experienced Any Adverse Event |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other |
|---|---|---|---|
| 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. |
| Measure Participants | 95 | 112 | 16 |
| Number [participants] |
90
94.7%
|
107
95.5%
|
16
100%
|
| Title | Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 215 |
| 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)
|
| Title | AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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 |
| Measure Participants | 163 |
| 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)
|
| Title | Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 141 |
| t1/2 at Dose 8, n=141 |
326
(0.56)
|
| t1/2 at Dose 12, n=81 |
277
(0.87)
|
| Title | Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 163 |
| CL at Dose 8, n=163 |
11.7
(0.48)
|
| CL at Dose 12, n=84 |
12.1
(1.23)
|
| Title | Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|
| 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. |
| Measure Participants | 133 |
| Vss at Dose 8, n=133 |
4.84
(0.30)
|
| Vss at Dose 12, n=83 |
3.73
(0.30)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other | |||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 60/95 (63.2%) | 59/112 (52.7%) | 12/16 (75%) | |||
| Blood and lymphatic system disorders | ||||||
| Neutropenia | 7/95 (7.4%) | 3/112 (2.7%) | 3/16 (18.8%) | |||
| Febrile neutropenia | 2/95 (2.1%) | 3/112 (2.7%) | 1/16 (6.3%) | |||
| Hemolytic anaemia | 0/95 (0%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Agranulocytosis | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Anemia | 2/95 (2.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Anemia haemolytic autoimmune | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Lymphocytic infiltration | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Thrombocytopenia | 4/95 (4.2%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Cardiac disorders | ||||||
| Myocardial infarction | 1/95 (1.1%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Myocardial ischaemia | 0/95 (0%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Cardic failure | 1/95 (1.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Myopericarditis | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Cardiac arrest | 0/95 (0%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Eye disorders | ||||||
| Diplopia | 1/95 (1.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Gastrointestinal disorders | ||||||
| Small intestinal obstruction | 1/95 (1.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Enteritis | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Ascites | 1/95 (1.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Abdominal pain | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Constipation | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Diarrhea | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Gastrointestinal pain | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| General disorders | ||||||
| Disease progression | 4/95 (4.2%) | 5/112 (4.5%) | 1/16 (6.3%) | |||
| Pyrexia | 6/95 (6.3%) | 4/112 (3.6%) | 0/16 (0%) | |||
| Hyperthermia | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Infusion related reaction | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Immune system disorders | ||||||
| Cytokine release syndrome | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Hypersensitivity | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Contrast media allergy | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Immunodeficiency | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 12/95 (12.6%) | 12/112 (10.7%) | 2/16 (12.5%) | |||
| Sepsis | 5/95 (5.3%) | 6/112 (5.4%) | 0/16 (0%) | |||
| Bronchopneumonia | 2/95 (2.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Herpes zoster | 2/95 (2.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Neutropenic sepsis | 4/95 (4.2%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Sinusitis | 2/95 (2.1%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Urinary tract infection | 2/95 (2.1%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Bronchitis | 2/95 (2.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Septic shock | 3/95 (3.2%) | 0/112 (0%) | 0/16 (0%) | |||
| Lobar pneumonia | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Appendicitis | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Aspergilloma | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Cellulitis | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Enterocolitis infection | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Folliculitis | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Fusarium infection | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Gastroenteritis | 1/95 (1.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Infection | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Injection site infection | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Lung infection | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Peritoneal infection | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Pneumocystis jiroveci pneumonia | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Pneumonia fungal | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Progessive multifocal | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Pseudomonas infection | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Upper respiratory tract infection | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Lower respiration infection | 0/95 (0%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Ear infection | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Eczema infected | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Erysipelas | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Enterocolitis infections | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Escherichia sepsis | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Eye infection staphylococcal | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Influenza | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Nocardiosis | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Pseuromonas infection | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Respiratory tract infection | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Accidental overdose | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Postoperative fever | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Transfusion reaction | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Lower limb fracture | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Spinal compression fracture | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Investigations | ||||||
| Blood lactate dehydrogenase increased | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Neutrophil count decreased | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Blood uric acid increased | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus inadequate control | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Hypercalcaemia | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Diabetes | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Hypokalemia | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Arthralgia | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Bone pain | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Breast cancer | 1/95 (1.1%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Chronic lympocytic leukaemia | 1/95 (1.1%) | 3/112 (2.7%) | 0/16 (0%) | |||
| Hodgkins disease | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Mantle cell lymphoma | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Chronic lymphocytic leukaemia transformation | 2/95 (2.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Bladder cancer | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Bowen's disease | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Colon cancer | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Neoplasm | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Skin cancer | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Squamous cell carcinoma of the skin | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Tumor lysis syndrome | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Nervous system disorders | ||||||
| Facial paresis | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Hemiparesis | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Ischaemic stroke | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Transient ischaemic attack | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Cerebral ischemia | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Epilepsy | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Psychiatric disorders | ||||||
| Confusional state | 2/95 (2.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Renal and urinary disorders | ||||||
| Urinary retention | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Haemoptysis | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Hypoxia | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Pleural effusion | 1/95 (1.1%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Pulmonary embolism | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Pulmonary edema | 0/95 (0%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Acute repiratory failure | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Bronchospasm | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Dyspnea | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Lung disorder | 0/95 (0%) | 1/112 (0.9%) | 0/16 (0%) | |||
| Lung infiltration | 0/95 (0%) | 0/112 (0%) | 1/16 (6.3%) | |||
| Respiratory failure | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Pyroderma gangrenosum | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Rash | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/95 (1.1%) | 2/112 (1.8%) | 0/16 (0%) | |||
| Haematoma | 1/95 (1.1%) | 0/112 (0%) | 0/16 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| 2000 mg Ofatumumab + DR | 2000 mg Ofatumumab + BFR | 2000 mg Ofatumumab + Other | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 90/95 (94.7%) | 107/112 (95.5%) | 16/16 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anemia | 17/95 (17.9%) | 20/112 (17.9%) | 2/16 (12.5%) | |||
| Neutropenia | 19/95 (20%) | 13/112 (11.6%) | 5/16 (31.3%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 16/95 (16.8%) | 16/112 (14.3%) | 5/16 (31.3%) | |||
| Nausea | 13/95 (13.7%) | 15/112 (13.4%) | 1/16 (6.3%) | |||
| Vomiting | 7/95 (7.4%) | 7/112 (6.3%) | 1/16 (6.3%) | |||
| Abdominal pain | 5/95 (5.3%) | 7/112 (6.3%) | 1/16 (6.3%) | |||
| General disorders | ||||||
| Fatigue | 12/95 (12.6%) | 22/112 (19.6%) | 1/16 (6.3%) | |||
| Pyrexia | 22/95 (23.2%) | 18/112 (16.1%) | 7/16 (43.8%) | |||
| Oedema peripheral | 9/95 (9.5%) | 14/112 (12.5%) | 1/16 (6.3%) | |||
| Chills | 13/95 (13.7%) | 13/112 (11.6%) | 2/16 (12.5%) | |||
| Infections and infestations | ||||||
| Pneumonia | 15/95 (15.8%) | 15/112 (13.4%) | 4/16 (25%) | |||
| Bronchitis | 14/95 (14.7%) | 12/112 (10.7%) | 0/16 (0%) | |||
| Upper respiratory tract infection | 4/95 (4.2%) | 17/112 (15.2%) | 2/16 (12.5%) | |||
| Nasopharyngitis | 10/95 (10.5%) | 10/112 (8.9%) | 1/16 (6.3%) | |||
| Herpes zoster | 6/95 (6.3%) | 6/112 (5.4%) | 0/16 (0%) | |||
| Sinusitis | 7/95 (7.4%) | 7/112 (6.3%) | 1/16 (6.3%) | |||
| Urinary tract infection | 4/95 (4.2%) | 8/112 (7.1%) | 1/16 (6.3%) | |||
| Lower respiratory tract infections | 5/95 (5.3%) | 6/112 (5.4%) | 3/16 (18.8%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 8/95 (8.4%) | 4/112 (3.6%) | 0/16 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 13/95 (13.7%) | 7/112 (6.3%) | 2/16 (12.5%) | |||
| Muscle spasms | 4/95 (4.2%) | 7/112 (6.3%) | 2/16 (12.5%) | |||
| Nervous system disorders | ||||||
| Headache | 8/95 (8.4%) | 5/112 (4.5%) | 1/16 (6.3%) | |||
| Parasthesia | 5/95 (5.3%) | 5/112 (4.5%) | 2/16 (12.5%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 7/95 (7.4%) | 7/112 (6.3%) | 1/16 (6.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 23/95 (24.2%) | 24/112 (21.4%) | 5/16 (31.3%) | |||
| Dyspnoea | 19/95 (20%) | 12/112 (10.7%) | 3/16 (18.8%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 17/95 (17.9%) | 8/112 (7.1%) | 5/16 (31.3%) | |||
| Urticaria | 5/95 (5.3%) | 9/112 (8%) | 2/16 (12.5%) | |||
| Hyperhidrosis | 6/95 (6.3%) | 8/112 (7.1%) | 1/16 (6.3%) | |||
| Vascular disorders | ||||||
| Hypotension | 7/95 (7.4%) | 6/112 (5.4%) | 1/16 (6.3%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00349349
Other Study ID Numbers:
- 111773
- Hx-CD20-406
First Posted:
Jul 7, 2006
Last Update Posted:
Jun 4, 2014
Last Verified:
Jun 1, 2013