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

Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment

Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).

Time frame: Time from randomization (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (assessed for a median of 8.7 weeks currently [or up to 13.3 months])

Overall Survival

OS is defined as the time from allocation to death. OS will also be subgrouped for responders and non-responders.

Time frame: Start of randomization (Week 0 of Visit 2) until death (up to a median of 17.1 weeks)

Percent Change From Baseline to Week 7 in Peripheral CD5+CD19+ Cell Counts

The peripheral blood for each participant was collected and analyzed for CD5+CD19+ cell counts. CD is "cluster of differentiation," is a cell surface marker for immunophenotyping, and, in this case, is a surrogate for B cell malignancy (indicates malignant B cells). Percent change from Visit 2 (Week 0, Baseline) = (value at Week 7 minus value at Week 0 divided by value at Week 0) x 100.

Time frame: Baseline (Visit 2) until Week 7 (Visit 9)

Percent Change From Baseline to Week 7 in Peripheral CD5+CD20+ Cell Counts

The peripheral blood for each participant was collected and analyzed for CD5+CD20+ cell counts. CD is "cluster of differentiation," is a cell surface marker for immunophenotyping, and, in this case, is a surrogate for B cell malignancy (indicates malignant B cells). Percent change from Visit 2 (Week 0, Baseline) = (value at Week 7 minus value at Week 0 divided by value at Week 0) x 100.

Time frame: Baseline (Visit 2) until Week 7 (Visit 9)

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) to Week 24 (Visit 14)

Tumor size and change in tumor size will be measured by the absolute value of and the percent change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24 (Visit 14). Percent change from Visit 2 (Baseline, Week 0) = (value at Week 24 minus value at Week 0 divided by value at Week 0) x 100.

Time frame: Baseline (Visit 2) until Week 24 (Visit 14)

Number of Participants With Complete Resolution of Constitutional Symptoms at Week 24

Participants with complete resolution of constitutional symptoms were those in whom no constitutional symptoms, such as night sweats, weight loss, and fever or extreme fatigue, were observed.

Time frame: Baseline (Visit 2) and Week 24

Number of Participants With Complete Resolution of Lymphadenopathy

Participants with complete resolution of lymphadenopathy (disease involving the lymph nodes) were defined as those in whom all observed lymph nodes were of normal size (all nodes \<1 centimeters) as determined by physical examination assessed by the investigator. All palpable lymph node sizes were recorded.

Time frame: Baseline (Visit 2) to end of study (up to Week 24)

Number of Participants With Improvement on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale at Week 24

ECOG performance status is a measure of the participant's ability to carry out activities of daily living on 6-point scale (0=fully active, 1=restricted in physically activity, ambulatory, 2=ambulatory \[\>50% of waking hours\], 3=capable of only limited self care, 4=completely disabled, 5=Dead). Improvement in ECOG performance status is defined as a decrease from baseline by at least one score on the ECOG scale.

Time frame: Baseline (Visit 2) and Week 24

Number of Participants Who Were Positive, Negative, or Had Missing Data for the Indicated Fluorescence in Situ Hybridization (FISH) Prognostic Factors at Screening

The number of participants (par.) who were positive, negative, or had missing data for the following prognostic factors indicative of altered responsiveness to treatment and/or survival was measured: 17p-, 11q-, +12q, 6q-, 13q-. Par. were assessed by FISH for these chromosomal abnormalities known tobe prognostic for time to treatment and survival when detected at diagnosis. Par. were categorized by the chromosomal abnormality detected: 17 p deletion, 11q deletion (but not 17 p deletion), 12 q trisomy (but not 17 p or 111q deletion), 13q deletion only, and no chromosomal abnormalities found.

Time frame: Screening (Visit 1, <=14 days prior to Visit 2)

Number of Participants With Improvement in Hemoglobin

The number of participants (par.) who had improvement in hemoglobin levels \>=11 grams (g)/deciliter (dl) (6.8 millimoles/liter) or 50% improvement over baseline was measured.

Time frame: Baseline (Visit 2) to Week 28

Number of Participants With Improvement in Thrombocytopenia (Thromb.)

Improvement in thromb. is defined as a decrease from Visit 2 by \>=1 National Cancer Institute Common Terminology Criteria (NCI CTC) grade. Thromb. is defined as low platelet counts resulting from refractory CLL, damage from prior treatment, advanced age, or reduced bone marrow function and can be considered as an adverse condition. Adverse events (AEs) such as thromb. in a cancer indication are graded on a scale determined by the NCI called the NCI CTC: lowest, grade 1; highest, grade 5 (death). Changes in this grading can assess improvements or declines in the severity of the AE.

Time frame: Baseline (Visit 2) to Week 28

Number of Participants With Complete Resolution of Hepatomegaly

Participants with complete resolution of enlarged liver (hepatomegaly) were defined as those with an enlarged palpable liver at baseline followed by the absence of hepatomegaly post- baseline (i.e., the liver was of normal size). Liver size was assessed by physical examination and documented as "centimeters" under the costal margin with relative changes in spleen size in 1 dimension calculated based on palpated numeric measurements (as per the 1996 NCIWG guidelines).

Time frame: Baseline (Visit 2) until Week 24

Number of Participants With Improvement in Neutropenia

Low levels of neutrophils (neutropenia) may increase the risk of developing serious infections and may be considered an adverse condition and evaluated on the NCI CTC with a grade. Improvement in neutropenia is defined as a decrease from Visit 2 (baseline) by at least one NCI CTC grade. Improvement is defined as a decrease from Visit 2 by at least one NCI CTC grade.

Time frame: Baseline (Visit 2) to Week 28

Number of Participants With Complete Resolution of Splenomegaly

Participants with complete resolution of enlarged spleen (splenomegaly) were defined as those with an enlarged palpable spleen at baseline followed by the absence of splenomegaly post-baseline (i.e., the spleen was of normal size). Spleen size was assessed by physical examination and documented as "centimeters" under the costal margin with relative changes in spleen size in 1 dimension calculated based on palpated numeric measurements (as per the 1996 NCIWG guidelines).

Time frame: Baseline (Visit 2) until Week 24

Number of Participants Who Experienced Any Adverse Event

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.

Time frame: From first infusion (Visit 2/Week 0) to Visit 21 (Month 24 of follow-up [up to Month 48]) or time of withdrawal (treatment and follow-up)

Cmax and Ctrough at Dose 1 (Visit 2, Week 0), Dose 8 (Visit 9, Week 7), and Dose 12 (Visit 14, Week 24)

Cmax is defined as the maximum concentration of drug in serum samples. Ctrough is defined as the trough serum concentration (measured concentration at the end of a dosing interval \[taken directly before the next administration\]). No drug was present before the first infusion; therefore, there are no Ctrough results for Dose 1

Time frame: Visit 2 (Week 0), Visit 9 (Week 7), and Visit 14 (Week 24)

AUC (0-inf) and AUC(0-tau) at Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)

AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-inf) is AUC from the start of infusion extrapolated to infinity. AUC(0-tau) is AUC from the start of infusion over the dosing interval.

Time frame: Visit 9 (Week 7) and Visit 14 (Week 24)

Half-life (t1/2) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)

Half-life ( t1/2) is defined as the terminal half-life and is the time required for the amount of drug in the body to decrease by half.

Time frame: Visit 9 (Week 7) and Visit14 (Week 24)

Clearance (CL) After Dose 8 (Visit 9, Week 7) and Dose 12 (Visit 14, Week 24)

CL is the clearance of drug from serum, which is defined as the volume of serum from which the drug is cleared per unit time.

Time frame: Visit 9 (Week 7) and Visit 14 (Week 24)

Volume of Distribution at Steady State (Vss) at Dose 8 (Visit 9, Week 7) and at Dose 12 (Visit 14, Week 24)

Vss is defined as the volume of distribution at steady state of ofatumumab.

Time frame: Visit 9 (Week 7) and Visit 14 (Week 24)