Ofatumumab 1000mg or should be diluted into 1000mL pyrogenefree saline and administered as an IV infusion.Duration of infusion will be approximately 6½ hours.Infusions should be given every 4 weeks until a total of 6 infusions has been given.

Fludarabine (25 mg/m2) should be administered as an IV infusion daily, Days 2 through 4 of Course 1, and Days 1 through 3 of Courses 2 through 6, every 4 weeks for 6 courses

Cyclophosphamide (250 mg/m2) should be administered as an IV infusion daily, Days 2 through 4 of Course 1, and Days 1 through 3 of Courses 2 through 6, every 4 weeks for 6 courses.

Progression-free survival (PFS) was defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

Time to next anti-CLL (anti-lymphoma) therapy was defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab or death. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.

Tumor size was measured by physical examination of palpable abnormal lymph nodes. Percent change from Baseline (Visit 2, Week 0) = (value at indicated visits minus value at Visit 2 divided by value at Visit 2) * 100. Visits 33, 34, 35, 36, and 37 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20.

Malignant B cells (CD5+CD19+ and CD5+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Screening (Visit 1, Week -2) = (value at indicated visits minus value at Visit 1 divided by value at Visit 1) * 100. Visits 33 and 34 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20.

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 this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.

HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 21, 35, and 39 for analysis of HAHA. Analysis of HAHA was done in batches.

Myelosuppression is one of the expected AEs for FC treatment and is defined as the decrease in the ability of the bone marrow to produce blood cells. The number of participants with myelosuppression was assessed from laboratory measurements with Grades 3(severe)-4 (life-threatening/disabling) (1, mild; 2, moderate; 5, death) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. The CTCAE is issued by the National Cancer Institute (NCI) and is the standard classification used for the severity grading scale for AEs in cancer therapy clinical studies.

Blood samples were drawn from participants at Visits 1 and 9 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 9 minus value at Visit 1 divided by value at Visit 1) * 100.

MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells (CD5+CD19+) to determine if there was any MRD.

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

AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-672) is AUC from start of infusion to 672 hours after start of infusion; AUC(0-inf) is AUC from start of infusion extrapolated to infinity.

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

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

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

Disease progression is characterized by at least one of the following, per the Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia: a >=50% increase in the sum of the products of at least two lymph nodes on two consecutive determinations 2 weeks apart (at least one node must be >=2 centimeters); or the appearance of new palpable lymph nodes; or a >=50% increase in liver and/or spleen size (measurement below the costal margin); or the appearance of palpable hepatomegaly or splenomegaly not previously present; or a >=50% increase in the numbers of circulating lymphocytes to at least 5.0 * 10^9/Liter; or transformation to a more aggressive histology (e.g., Richter's syndrome or prolymphocytic leukemia with >55% prolymphocytes). For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

Total of all reporting groups

Ofatumumab iv infusion initiated at 300 mg for course 1, followed by dose of 1000 mg for courses 2-6 in combination with fludarabine iv (25 mg/m^2 daily on Days 1-3) and cyclophosphamide iv (250 mg/m^2 daily on Days 1-3) administered every 4 weeks for a total of 6 courses

The duration of response was defined as the time from the initial response (the first visit at which response was observed) to progression or death. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed.

FAS. Only those participants classified as responders were analyzed.

Progression-free survival (PFS) was defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

FAS

Time to next anti-CLL (anti-lymphoma) therapy was defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab or death. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.

FAS

Tumor size was measured by physical examination of palpable abnormal lymph nodes. Percent change from Baseline (Visit 2, Week 0) = (value at indicated visits minus value at Visit 2 divided by value at Visit 2) * 100. Visits 33, 34, 35, 36, and 37 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20.

FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Malignant B cells (CD5+CD19+ and CD5+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Screening (Visit 1, Week -2) = (value at indicated visits minus value at Visit 1 divided by value at Visit 1) * 100. Visits 33 and 34 are measured in the number of months from the start of the last infusion. The start of the last infusion could have occurred up to Week 20.

FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

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 this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.

FAS

HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 21, 35, and 39 for analysis of HAHA. Analysis of HAHA was done in batches.

FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Myelosuppression is one of the expected AEs for FC treatment and is defined as the decrease in the ability of the bone marrow to produce blood cells. The number of participants with myelosuppression was assessed from laboratory measurements with Grades 3(severe)-4 (life-threatening/disabling) (1, mild; 2, moderate; 5, death) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. The CTCAE is issued by the National Cancer Institute (NCI) and is the standard classification used for the severity grading scale for AEs in cancer therapy clinical studies.

FAS

Blood samples were drawn from participants at Visits 1 and 9 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 9 minus value at Visit 1 divided by value at Visit 1) * 100.

FAS. Data were provided for the number of participants attending Visit 9. Participants withdrawn during the study were not analyzed.

Par. were evaluated by an IRC in accordance with NCI-WG 1996 guideline. Responders: CR, Nodular Partial Remission (nPR, same as CR, but persistent bone marrow nodules), and Partial Remission (PR, >=50% decrease in lymphocytes from pretreatment baseline (BL) value, >=50% reduction in lymphadenopathy, >=50% reduction of liver/spleen and neutrophils >= 1.5*10^9/L or platelets >100*10^9/L or hemoglobin >11 g/dL (or 50% improvement over BL for neutrophils, platelets, hemoglobin); non-responders: Stable Disease (SD, did not achieve CR/PR, and no PD), Progressive Disease (PD), or Not Evaluable (NE).

FAS

MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells (CD5+CD19+) to determine if there was any MRD.

FAS. Only participants with CR at Visit 34 were analyzed.

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

FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-672) is AUC from start of infusion to 672 hours after start of infusion; AUC(0-inf) is AUC from start of infusion extrapolated to infinity.

FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

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

FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

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

FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

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

FAS. Data were provided for the number of participants attending each visit for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed.

Disease progression is characterized by at least one of the following, per the Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia: a >=50% increase in the sum of the products of at least two lymph nodes on two consecutive determinations 2 weeks apart (at least one node must be >=2 centimeters); or the appearance of new palpable lymph nodes; or a >=50% increase in liver and/or spleen size (measurement below the costal margin); or the appearance of palpable hepatomegaly or splenomegaly not previously present; or a >=50% increase in the numbers of circulating lymphocytes to at least 5.0 * 10^9/Liter; or transformation to a more aggressive histology (e.g., Richter's syndrome or prolymphocytic leukemia with >55% prolymphocytes). For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

FAS

Ofatumumab iv infusion initiated at 300 mg for course 1, followed by dose of 1000 mg for courses 2-6 in combination with fludarabine iv (25 mg/m^2 daily on Days 1-3) and cyclophosphamide iv (250 mg/m^2 daily on Days 1-3) administered every 4 weeks for a total of 6 courses

Participants were monitored in the Extended Follow-up Phase every 6 months for survival until alternative Chronic Lymphocyte Leukemia (CLL) therapy was initiated, or until Month 60.

Participants were monitored in the Extended Follow-up Phase every 6 months for survival until alternative CLL therapy was initiated, or until Month 60.