A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00811733

Collaborator

(none)

Enrollment

Locations

Arm

59.1

Duration (Months)

5.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Given the tolerability and efficacy of ofatumumab in follicular lymphoma and Chronic Lymphocytic Leukemia, and the need to improve therapy for patients with WM utilizing a non-myelosuppressive agent this phase II trial of ofatumumab is being initiated in patients with Waldenstrom's Macroglobulinemia (WM).

Condition or Disease	Intervention/Treatment	Phase
Waldenstrom Macroglobulinaemia	Biological: Ofatumumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia

Study Start Date :

Mar 1, 2009

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ofatumumab Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.	Biological: Ofatumumab Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.

Arm

Intervention/Treatment

Experimental: Ofatumumab

Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.

Biological: Ofatumumab

Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.

Outcome Measures

Primary Outcome Measures

Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator [Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment]
OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator [Baseline and up to Study Week 16]
OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.

Secondary Outcome Measures

Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator [Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment]
Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator [Baseline and up to Study Week 16]
Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle) [Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment]
IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by >25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of >25% from BL.
Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator [From baseline up to approximately 5 years]
Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node >=1.5 centimeters on any axis. Progression for PR/MR is either a >=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM.
Progression-free Survival [From baseline up to approximately 5 years]
Time to disease progression is defined as the time from baseline to disease progression or death.
Time to Response for Responders [From baseline up to approximately 5 years]
Time to response is defined as the time from baseline to the first response date.
Overall Survival [From baseline up to approximately 5 years]
Overall survival is defined as the time from baseline until death due to any cause.
Clearance of Ofatumumab [From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7]
Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Volume of Distribution at Steady State of Ofatumumab [From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7]
Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Half-life of Ofatumumab [From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7]
Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Cmax and Ctrough of Ofatumumab [From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7]
Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
AUC(0-tau) and AUC(0-inf) of Ofatumumab [From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7]
AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result [From baseline up to approximately 5 years]
All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive.
Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment [Baseline and Month 3]
CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Number of Participants With the Indicated SAEs Related to Study Drug [From baseline up to approximately 5 years]
An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug [From baseline up to approximately 5 years]
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug.
Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study [From baseline up to approximately 5 years]
Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study.
Number of Participants With the Indicated >=Grade 3 AEs [From baseline up to approximately 5 years]
AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Number of Participants With the Indicated Infusion-related >=Grade 3 AE [From baseline up to approximately 5 years]
Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed and active Waldenstrom's Macroglobulinemia requiring treatment.
Ambulatory and capable of all selfcare. Up and about more than 50% of waking hours.
Adequate organ function.
Detectable CD20 positive of the tumor cells.
Measurable disease as defined by a monoclonal IgM paraprotein level greater than 1000 mg/dL.

Exclusion Criteria:

Treatment of WM within the past 28 days.
Treatment with rituximab or alemtuzamab within the past 3 months.
Certain heart problems, chronic or current active infection not controlled with oral antibiotics, other current cancer or within last 5 years.
Current participation in another interventional clinical study.
Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception.
Active cerebrovascular disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Los Angeles	California	United States	90095-6984
2	GSK Investigational Site	Stanford	California	United States	94305
3	GSK Investigational Site	Rochester	Minnesota	United States	55905
4	GSK Investigational Site	Buffalo	New York	United States	14263
5	GSK Investigational Site	New York	New York	United States	10021
6	GSK Investigational Site	Columbus	Ohio	United States	43210-1228
7	GSK Investigational Site	San Antonio	Texas	United States	78229

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00811733

Other Study ID Numbers:

110921

First Posted:

Dec 19, 2008

Last Update Posted:

May 30, 2017

Last Verified:

Mar 1, 2015

Keywords provided by GlaxoSmithKline

Waldenstrom's Macroglobulinemia

Ofatumumab

Additional relevant MeSH terms:

Waldenstrom Macroglobulinemia

Ofatumumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Period Title: Overall Study
STARTED	15	22
COMPLETED	4	12
NOT COMPLETED	11	10

Baseline Characteristics

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5	Total
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.	Total of all reporting groups
Overall Participants	15	22	37
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.3 (10.78)	64.0 (9.36)	63.3 (9.85)
Sex: Female, Male (Count of Participants)
Female	6 40%	9 40.9%	15 40.5%
Male	9 60%	13 59.1%	22 59.5%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	0 0%	1 4.5%	1 2.7%
Asian - East Asian Heritage	0 0%	1 4.5%	1 2.7%
White - White/Caucasian/European	14 93.3%	19 86.4%	33 89.2%
Unknown	1 6.7%	1 4.5%	2 5.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator
Description	OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Time Frame	Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were considered eligible for treatment and who had been exposed to study drug irrespective of the planned course of treatment.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
Number [participants]	7 46.7%	15 68.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	47
	Confidence Interval	(2-Sided) 95% 21.3 to 73.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the percentage of participants with OR.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	68
	Confidence Interval	(2-Sided) 95% 45.1 to 86.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the percentage of participants with OR.

2. Primary Outcome

Title	Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator
Description	OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Time Frame	Baseline and up to Study Week 16

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
Number [participants]	5 33.3%	14 63.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	33
	Confidence Interval	(2-Sided) 95% 11.8 to 61.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the percentage of participants with OR.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	64
	Confidence Interval	(2-Sided) 95% 40.7 to 82.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the percentage of participants with OR.

3. Secondary Outcome

Title	Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator
Description	Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Time Frame	Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
CR	0 0%	0 0%
PR	4 26.7%	11 50%
MR	3 20%	4 18.2%

4. Secondary Outcome

Title	Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator
Description	Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Time Frame	Baseline and up to Study Week 16

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
CR	0 0%	0 0%
PR	3 20%	9 40.9%
MR	2 13.3%	5 22.7%

5. Secondary Outcome

Title	Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle)
Description	IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by >25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of >25% from BL.
Time Frame	Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants who received Cycle 1 treatment (including the Redosing Cycle) were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
>25% increase from BL, any response, n=15, 22	7 46.7%	9 40.9%
=<25% increase from BL, any response, n=15, 22	8 53.3%	13 59.1%
>25% increase from BL, PR/MR response , n=7, 15	1 6.7%	2 9.1%
=<25% increase from BL, PR/MR response , n=7, 15	6 40%	13 59.1%

6. Secondary Outcome

Title	Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator
Description	Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node >=1.5 centimeters on any axis. Progression for PR/MR is either a >=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants classified as responders were included in the analysis. Participants who had disease progression or death were counted as events, and other participants were censored at the date of the last adequate assessment in the study.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	7	15
Measure events	5	9
Median (Inter-Quartile Range) [days]	449.0	455.0

7. Secondary Outcome

Title	Progression-free Survival
Description	Time to disease progression is defined as the time from baseline to disease progression or death.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
ITT Population. Participants who experienced disease progression or death were counted as events, and other participants were censored at the time of the last adequate assessment in the study.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
Measure events	8	13
Median (Inter-Quartile Range) [days]	558.0	536.0

8. Secondary Outcome

Title	Time to Response for Responders
Description	Time to response is defined as the time from baseline to the first response date.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
ITT Population. Only participants classified as responders (CR, PR, and MR) were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	7	15
Median (95% Confidence Interval) [days]	78	81

9. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from baseline until death due to any cause.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants who died during the study and during the follow-up period were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	0	0

10. Secondary Outcome

Title	Clearance of Ofatumumab
Description	Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time Frame	From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Population: all participants from whom a PK sample was obtained and analyzed. Data were provided for the number of participants for whom the parameter could be determined.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	21
Geometric Mean (95% Confidence Interval) [milliliters/hour (ml/hr)]	27.9	13.5

11. Secondary Outcome

Title	Volume of Distribution at Steady State of Ofatumumab
Description	Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time Frame	From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7

Outcome Measure Data

Analysis Population Description
PK Population. Data were provided for the number of participants for whom the parameter could be determined.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	21
Geometric Mean (95% Confidence Interval) [Liters (L)]	10.0	10.7

12. Secondary Outcome

Title	Half-life of Ofatumumab
Description	Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time Frame	From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7

Outcome Measure Data

Analysis Population Description
PK Population. Data were provided for the number of participants for whom the parameter could be determined.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	21
Geometric Mean (95% Confidence Interval) [Days (d)]	10.9	23.9

13. Secondary Outcome

Title	Cmax and Ctrough of Ofatumumab
Description	Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time Frame	From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7

Outcome Measure Data

Analysis Population Description
PK Population. Data were provided for the number of participants attending each visit for whom the parameter could be determined.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	21
Cmax, Course 1 Dose 1, n=14,19	68.3	72.1
Cmax, Course 1 Dose 3, n=0,19	NA	465
Cmax, Course 1 Dose 4, n=13,0	259	NA
Cmax, Course 1 Dose 5, n=0,18	NA	640
Ctrough, Course 1 Dose 2, n=7,12	3.0	8.0
Ctrough, Course 1 Dose 3, n=11,19	13.9	121
Ctrough, Course 1 Dose 4, n=13,21	23.4	181
Ctrough, Course 1 Dose 5, n=0,18	NA	249
Cmax, Course 2 Dose 1, n=9,11	53.2	64.8
Cmax, Course 2 Dose 3, n=8,12	554	577
Cmax, Course 2 Dose 5, n=10,12	528	803
Ctrough, Course 2 Dose 2, n=7,10	8.1	20.4
Ctrough, Course 2 Dose 3, n=8,12	144	169
Ctrough, Course 2 Dose 4, n=11,12	225	310
Ctrough, Course 2 Dose 5, n=11,12	279	384

14. Secondary Outcome

Title	AUC(0-tau) and AUC(0-inf) of Ofatumumab
Description	AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
Time Frame	From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7

Outcome Measure Data

Analysis Population Description
PK Population. Data were provided for the number of participants attending each visit for whom the parameter could be calculated..

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	21
AUC(0-tau), Course 1 Dose 4, n=13,0	21419	NA
AUC(0-tau), Course 1 Dose 5, n=0,18	NA	75526
AUC(0-inf), Course 1 Dose 4, n=9,0	120886	NA
AUC(0-inf), Course 1 Dose 5, n=0,18	NA	392012
AUC(0-tau), Course 2 Dose 5, n=10,12	61259	106275
AUC(0-inf), Course 2 Dose 5, n=8,12	221675	507794

15. Secondary Outcome

Title	Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result
Description	All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with post-ofatumumab HAHA results were analyzed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	11	20
Number [participants]	1 6.7%	4 18.2%

16. Secondary Outcome

Title	Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment
Description	CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline and Month 3

Outcome Measure Data

Analysis Population Description
ITT Population: only participants with blood count data at both Baseline and Month 3 were included in the analysis.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	15	22
CD4+	-35.5	98
CD19+	-26	-24.5
CD50	9	-43

17. Secondary Outcome

Title	Number of Participants With the Indicated SAEs Related to Study Drug
Description	An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants who experienced an SAE categorized as being related to study drug were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	2	2
Haemolysis	0 0%	1 4.5%
Chest pain	0 0%	1 4.5%
Cryoglobulinaemia	1 6.7%	0 0%
Fluid overload	0 0%	1 4.5%
Renal failure acute	1 6.7%	0 0%
Pulmonary oedema	0 0%	1 4.5%

18. Secondary Outcome

Title	Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants who experienced a study drug-related AE were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	13	22
Pruritus	4 26.7%	8 36.4%
Urticaria	4 26.7%	9 40.9%
Rash	4 26.7%	3 13.6%
Pruritus generalised	2 13.3%	1 4.5%
Hyperhidrosis	1 6.7%	1 4.5%
Erythema	1 6.7%	0 0%
Palmar erythema	0 0%	1 4.5%
Rash macular	1 6.7%	0 0%
Swelling face	0 0%	1 4.5%
Throat irritation	7 46.7%	3 13.6%
Nasal congestion	1 6.7%	2 9.1%
Oropharyngeal pain	0 0%	3 13.6%
Dyspnoea	0 0%	1 4.5%
Epistaxis	0 0%	1 4.5%
Painful respiration	0 0%	1 4.5%
Pulmonary oedema	0 0%	1 4.5%
Rhinitis allergic	0 0%	1 4.5%
Rhinorrhoea	1 6.7%	0 0%
Sneezing	0 0%	1 4.5%
Pyrexia	2 13.3%	5 22.7%
Chills	1 6.7%	5 22.7%
Chest pain	1 6.7%	1 4.5%
Chest discomfort	2 13.3%	0 0%
Fatigue	1 6.7%	2 9.1%
Non-cardiac chest pain	2 13.3%	0 0%
Asthenia	0 0%	1 4.5%
Ill-defined disorder	1 6.7%	0 0%
Local swelling	0 0%	1 4.5%
Malaise	0 0%	1 4.5%
Pain	1 6.7%	0 0%
Abdominal pain	2 13.3%	1 4.5%
Diarrhoea	0 0%	3 13.6%
Nausea	0 0%	2 9.1%
Paraesthesia oral	0 0%	2 9.1%
Abdominal discomfort	1 6.7%	0 0%
Dyspepsia	1 6.7%	0 0%
Hypoaesthesia oral	0 0%	1 4.5%
Lip swelling	1 6.7%	0 0%
Oral pain	0 0%	1 4.5%
Oral pruritus	0 0%	1 4.5%
Stomatitis	0 0%	1 4.5%
Flushing	6 40%	4 18.2%
Hypotension	0 0%	1 4.5%
Back pain	1 6.7%	1 4.5%
Limb discomfort	0 0%	1 4.5%
Muscle spasms	1 6.7%	0 0%
Musculoskeletal pain	1 6.7%	0 0%
Myalgia	0 0%	2 9.1%
Trismus	1 6.7%	0 0%
Anaemia	0 0%	2 9.1%
Haemolysis	1 6.7%	1 4.5%
Leukopenia	0 0%	1 4.5%
Lymph node pain	1 6.7%	0 0%
Neutropenia	0 0%	1 4.5%
Ear pruritus	3 20%	2 9.1%
Eye pruritus	3 20%	0 0%
Ocular hyperaemia	1 6.7%	1 4.5%
Abnormal sensation in eye	0 0%	1 4.5%
Eye swelling	0 0%	1 4.5%
Decreased appetite	2 13.3%	1 4.5%
Fluid overload	0 0%	1 4.5%
Hypophagia	0 0%	1 4.5%
Increased appetite	0 0%	1 4.5%
Headache	1 6.7%	1 4.5%
Paraesthesia	0 0%	2 9.1%
Sinus headache	1 6.7%	0 0%
Infusion related reaction	2 13.3%	3 13.6%
Blood creatinine increased	1 6.7%	0 0%
Body temperature increased	0 0%	1 4.5%
Protein total increased	0 0%	1 4.5%
Hypersensitivity	0 0%	1 4.5%
Serum sickness	1 6.7%	0 0%
Rhinitis	1 6.7%	0 0%
Urinary tract infection	0 0%	1 4.5%
Bradycardia	1 6.7%	0 0%
Insomnia	0 0%	1 4.5%
Renal failure acute	1 6.7%	0 0%
Thirst	1 6.7%	0 0%
Vomiting	0 0%	1 4.5%
Cryoglobulinaemia	1 6.7%	0 0%
Pallor	1 6.7%	0 0%
Arthralgia	1 6.7%	1 4.5%
Fluid retention	1 6.7%	0 0%
Hypoaesthesia	0 0%	1 4.5%
Psychomotor hyperactivity	0 0%	1 4.5%
Weight decreased	1 6.7%	0 0%

19. Secondary Outcome

Title	Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study
Description	Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants who experienced an AE leading to their withdrawal from the study were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	2	1
Haemolysis	1 6.7%	1 4.5%
Febrile neutropenia	1 6.7%	0 0%
Myocardial ischaemia	0 0%	1 4.5%
Fluid overload	0 0%	1 4.5%
Renal failure acute	1 6.7%	0 0%
Pulmonary oedema	0 0%	1 4.5%
Haemolytic anaemia	0 0%	1 4.5%

20. Secondary Outcome

Title	Number of Participants With the Indicated >=Grade 3 AEs
Description	AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants who experienced a >=Grade 3 AE were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	8	8
Haemolysis	1 6.7%	1 4.5%
Anaemia	1 6.7%	0 0%
Febrile neutropenia	1 6.7%	0 0%
Haemolytic anaemia	0 0%	1 4.5%
Chest pain	1 6.7%	1 4.5%
Chest discomfort	1 6.7%	0 0%
Pyrexia	0 0%	1 4.5%
Blood creatinine increased	1 6.7%	0 0%
Haemoglobin decreased	0 0%	1 4.5%
Protein total increased	0 0%	1 4.5%
Dyspnoea exertional	0 0%	1 4.5%
Epistaxis	1 6.7%	0 0%
Pulmonary oedema	0 0%	1 4.5%
Cryoglobulinaemia	1 6.7%	0 0%
Serum sickness	1 6.7%	0 0%
Dizziness	0 0%	1 4.5%
Headache	1 6.7%	0 0%
Syncope	0 0%	1 4.5%
Myocardial ischaemia	0 0%	1 4.5%
Abdominal discomfort	1 6.7%	0 0%
Urinary tract infection	0 0%	1 4.5%
Fluid overload	0 0%	1 4.5%
Back pain	0 0%	1 4.5%
Renal failure acute	1 6.7%	0 0%
Rash	1 6.7%	0 0%
Neutropenia	1 6.7%	1 4.5%
Fatigue	0 0%	1 4.5%
Small intestinal obstruction	0 0%	1 4.5%

21. Secondary Outcome

Title	Number of Participants With the Indicated Infusion-related >=Grade 3 AE
Description	Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Time Frame	From baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants who experienced >=Grade 3 infusion-related AEs were assessed.

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5	300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.	Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
Measure Participants	2	2
Chest pain	1 6.7%	1 4.5%
Chest discomfort	1 6.7%	0 0%
Back pain	0 0%	1 4.5%
Rash	1 6.7%	0 0%

Adverse Events

	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5		300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Time Frame	Participants were followed from baseline up to approximately 5 years.
Adverse Event Reporting Description

Arm/Group Title	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5		300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
Arm/Group Description	Participants received ofatumumab intravenously (IV) in Cycle 1 (defined as a treatment period of up to 4 weeks [Weeks (Wk.) 1 through 4]) (300 milligrams [mg] at Week 1 and 1000 mg at Weeks 2 through 4) and were followed up for 11 weeks (Weeks 5-16). After Week 16, during the Redosing Cycle (RC), participants who had Minor Response or stable disease after Cycle 1 and had not received another Waldenstrom's Macroglobulinemia (WM) therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response in either Cycle 1 or the RC and subsequently progressed before 36 months entered Cycle 2 of treatment and received IV ofatumumab 300 mg at Week 1 and IV ofatumumab 2000 mg during Weeks 2 through 5.		Participants received ofatumumab IV at 300 mg at Week 1 and 2000 mg at Weeks 2 through 5 in Cycle 1 (defined as a treatment period of up to 5 weeks [Weeks 1 through 5]) and were followed up for 10 weeks (Weeks 6-16). After Week 16, during the RC, participants who had Minor Response or stable disease after Cycle 1 and had not received another WM therapy received 300 mg IV ofatumumab at Week 1 and 2000 mg IV ofatumumab at Weeks 2 through 5. Participants who achieved a response and subsequently progressed before 36 months entered Cycle 2 of treatment and received 300 mg at Week 1 and 2000 mg during Weeks 2 through 5.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5		300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)		7/22 (31.8%)
Blood and lymphatic system disorders
Haemolysis	1/15 (6.7%)		1/22 (4.5%)
Anaemia	1/15 (6.7%)		0/22 (0%)
Febrile neutropenia	1/15 (6.7%)		0/22 (0%)
Haemolytic anaemia	0/15 (0%)		1/22 (4.5%)
Cardiac disorders
Cardiac failure	0/15 (0%)		1/22 (4.5%)
Myocardial ischaemia	0/15 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Gingival bleeding	1/15 (6.7%)		0/22 (0%)
Small intestinal obstruction	0/15 (0%)		1/22 (4.5%)
General disorders
Catheter site haemorrhage	1/15 (6.7%)		0/22 (0%)
Chest pain	0/15 (0%)		1/22 (4.5%)
Fatigue	0/15 (0%)		1/22 (4.5%)
Pyrexia	0/15 (0%)		2/22 (9.1%)
Immune system disorders
Cryoglobulinaemia	1/15 (6.7%)		0/22 (0%)
Infections and infestations
Bacteraemia	0/15 (0%)		1/22 (4.5%)
Injury, poisoning and procedural complications
Hip fracture	1/15 (6.7%)		0/22 (0%)
Metabolism and nutrition disorders
Fluid overload	0/15 (0%)		1/22 (4.5%)
Nervous system disorders
Syncope	1/15 (6.7%)		0/22 (0%)
Renal and urinary disorders
Renal failure acute	1/15 (6.7%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional	0/15 (0%)		1/22 (4.5%)
Epistaxis	1/15 (6.7%)		0/22 (0%)
Pleural effusion	0/15 (0%)		1/22 (4.5%)
Pulmonary oedema	0/15 (0%)		1/22 (4.5%)
Other (Not Including Serious) Adverse Events
	300 mg Ofatumumab, Wk. 1; 1000/2000 mg Ofatumumab, Wk. 2-4/2-5		300 mg Ofatumumab, Wk. 1; 2000 mg Ofatumumab, Wk. 2-5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		20/22 (90.9%)
Blood and lymphatic system disorders
Anaemia	0/15 (0%)		2/22 (9.1%)
Neutropenia	1/15 (6.7%)		1/22 (4.5%)
Lymph node pain	1/15 (6.7%)		0/22 (0%)
Cardiac disorders
Palpitations	1/15 (6.7%)		1/22 (4.5%)
Bradycardia	1/15 (6.7%)		0/22 (0%)
Congenital, familial and genetic disorders
Von Willebrand's disease	1/15 (6.7%)		0/22 (0%)
Ear and labyrinth disorders
Ear pruritus	3/15 (20%)		3/22 (13.6%)
Deafness	1/15 (6.7%)		0/22 (0%)
Eye disorders
Eye pruritus	3/15 (20%)		0/22 (0%)
Ocular hyperaemia	1/15 (6.7%)		1/22 (4.5%)
Gastrointestinal disorders
Abdominal pain	3/15 (20%)		2/22 (9.1%)
Constipation	2/15 (13.3%)		2/22 (9.1%)
Diarrhea	2/15 (13.3%)		3/22 (13.6%)
Dyspepsia	2/15 (13.3%)		1/22 (4.5%)
Gastrooesophageal reflux disease	2/15 (13.3%)		0/22 (0%)
Hypoaesthesia oral	0/15 (0%)		2/22 (9.1%)
Nausea	0/15 (0%)		2/22 (9.1%)
Paraesthesia oral	0/15 (0%)		2/22 (9.1%)
Stomatitis	1/15 (6.7%)		1/22 (4.5%)
Abdominal discomfort	1/15 (6.7%)		0/22 (0%)
Abdominal distension	1/15 (6.7%)		0/22 (0%)
Lip swelling	1/15 (6.7%)		0/22 (0%)
Mouth ulceration	1/15 (6.7%)		0/22 (0%)
Toothache	1/15 (6.7%)		0/22 (0%)
Vomiting	1/15 (6.7%)		1/22 (4.5%)
Tongue ulceration	1/15 (6.7%)		0/22 (0%)
General disorders
Pyrexia	3/15 (20%)		5/22 (22.7%)
Fatigue	4/15 (26.7%)		4/22 (18.2%)
Chills	1/15 (6.7%)		5/22 (22.7%)
Asthenia	0/15 (0%)		3/22 (13.6%)
Chest pain	1/15 (6.7%)		2/22 (9.1%)
Chest discomfort	2/15 (13.3%)		0/22 (0%)
Non-cardiac chest pain	2/15 (13.3%)		0/22 (0%)
Oedema	0/15 (0%)		2/22 (9.1%)
Oedema peripheral	2/15 (13.3%)		0/22 (0%)
Ill-defined disorder	1/15 (6.7%)		0/22 (0%)
Medical device pain	1/15 (6.7%)		0/22 (0%)
Pain	1/15 (6.7%)		0/22 (0%)
Thirst	1/15 (6.7%)		0/22 (0%)
Immune system disorders
Seasonal allergy	1/15 (6.7%)		0/22 (0%)
Serum sickness	1/15 (6.7%)		0/22 (0%)
Infections and infestations
Upper respiratory tract infection	7/15 (46.7%)		2/22 (9.1%)
Sinusitis	2/15 (13.3%)		3/22 (13.6%)
Urinary tract infection	3/15 (20%)		1/22 (4.5%)
Nasopharyngitis	2/15 (13.3%)		0/22 (0%)
Pneumonia	2/15 (13.3%)		0/22 (0%)
Bronchitis	1/15 (6.7%)		0/22 (0%)
Rhinitis	1/15 (6.7%)		0/22 (0%)
Candida infection	1/15 (6.7%)		0/22 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	2/15 (13.3%)		3/22 (13.6%)
Investigations
Blood creatine phosphokinase increased	1/15 (6.7%)		0/22 (0%)
Blood creatinine increased	1/15 (6.7%)		0/22 (0%)
Blood parathyroid hormone increased	1/15 (6.7%)		0/22 (0%)
Weight decreased	1/15 (6.7%)		0/22 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/15 (20%)		2/22 (9.1%)
Hyperglycaemia	1/15 (6.7%)		3/22 (13.6%)
Hyponatraemia	0/15 (0%)		2/22 (9.1%)
Iron deficiency	1/15 (6.7%)		1/22 (4.5%)
Haemochromatosis	1/15 (6.7%)		0/22 (0%)
Hypercalcaemia	1/15 (6.7%)		0/22 (0%)
Fluid retention	1/15 (6.7%)		0/22 (0%)
Hyperuricaemia	1/15 (6.7%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	4/15 (26.7%)		1/22 (4.5%)
Myalgia	1/15 (6.7%)		4/22 (18.2%)
Arthralgia	1/15 (6.7%)		3/22 (13.6%)
Back pain	1/15 (6.7%)		1/22 (4.5%)
Pain in extremity	1/15 (6.7%)		1/22 (4.5%)
Arthritis	1/15 (6.7%)		0/22 (0%)
Bone pain	1/15 (6.7%)		0/22 (0%)
Muscular weakness	1/15 (6.7%)		0/22 (0%)
Muscular pain	1/15 (6.7%)		1/22 (4.5%)
Trismus	1/15 (6.7%)		0/22 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/15 (6.7%)		0/22 (0%)
Nervous system disorders
Headache	5/15 (33.3%)		4/22 (18.2%)
Paraesthesia	1/15 (6.7%)		3/22 (13.6%)
Dizziness	1/15 (6.7%)		2/22 (9.1%)
Hypoaesthesia	1/15 (6.7%)		2/22 (9.1%)
Tremor	1/15 (6.7%)		1/22 (4.5%)
Polyneuropathy	1/15 (6.7%)		0/22 (0%)
Restless legs syndrome	1/15 (6.7%)		0/22 (0%)
Neuropathy peripheral	1/15 (6.7%)		2/22 (9.1%)
Sinus headache	1/15 (6.7%)		2/22 (9.1%)
Psychiatric disorders
Insomnia	2/15 (13.3%)		4/22 (18.2%)
Depression	1/15 (6.7%)		0/22 (0%)
Libido decreased	1/15 (6.7%)		0/22 (0%)
Renal and urinary disorders
Nocturia	1/15 (6.7%)		0/22 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/15 (6.7%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Throat irritation	7/15 (46.7%)		3/22 (13.6%)
Oropharyngeal pain	2/15 (13.3%)		5/22 (22.7%)
Cough	4/15 (26.7%)		2/22 (9.1%)
Epistaxis	3/15 (20%)		3/22 (13.6%)
Nasal congestion	3/15 (20%)		3/22 (13.6%)
Dyspnoea	1/15 (6.7%)		2/22 (9.1%)
Dysphonia	1/15 (6.7%)		1/22 (4.5%)
Rhinorrhoea	1/15 (6.7%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Pruritus	5/15 (33.3%)		8/22 (36.4%)
Urticaria	4/15 (26.7%)		9/22 (40.9%)
Rash	6/15 (40%)		3/22 (13.6%)
Pruritus generalised	2/15 (13.3%)		1/22 (4.5%)
Hyperhidrosis	1/15 (6.7%)		1/22 (4.5%)
Erythema	1/15 (6.7%)		0/22 (0%)
Haemorrhage subcutaneous	1/15 (6.7%)		0/22 (0%)
Nail bed bleeding	1/15 (6.7%)		0/22 (0%)
Rash macular	1/15 (6.7%)		0/22 (0%)
Acne	1/15 (6.7%)		0/22 (0%)
Vascular disorders
Flushing	6/15 (40%)		4/22 (18.2%)
Hot flush	1/15 (6.7%)		0/22 (0%)
Pallor	1/15 (6.7%)		0/22 (0%)
Raynaud's phenomenon	1/15 (6.7%)		0/22 (0%)

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
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00811733

Other Study ID Numbers:

110921

First Posted:

Dec 19, 2008

Last Update Posted:

May 30, 2017

Last Verified:

Mar 1, 2015

A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact