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

Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator

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

Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle)

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

Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator

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

Progression-free Survival

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

Time to Response for Responders

Time to response is defined as the time from baseline to the first response date.

Time frame: From baseline up to approximately 5 years

Overall Survival

Overall survival is defined as the time from baseline until death due to any cause.

Time frame: From baseline up to approximately 5 years

Clearance of Ofatumumab

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

Volume of Distribution at Steady State of Ofatumumab

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

Half-life of Ofatumumab

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

Cmax and Ctrough of Ofatumumab

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

AUC(0-tau) and AUC(0-inf) of Ofatumumab

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

Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result

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

Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment

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

Number of Participants With the Indicated SAEs Related to Study Drug

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

Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug

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

Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study

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

Number of Participants With the Indicated >=Grade 3 AEs

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

Number of Participants With the Indicated Infusion-related >=Grade 3 AE

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