Trial Outcomes & Findings for Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia (NCT NCT00748189)

Last Updated: 2019-06-25

Results Overview

PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months

Results posted on

2019-06-25

Participant Flow

Eligible participants (par.) were stratified by age (\<65 years vs. \>=65years), stage (Binet A vs. B vs. C) and Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2). Participants in each stratum were then centrally randomized in a 1:1 ratio to receive ofatumumab plus chlorambucil (O+CHL) or chlorambucil alone (CHL).

Participant milestones

Participant milestones
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Overall Study STARTED	226	221
Overall Study COMPLETED	10	9
Overall Study NOT COMPLETED	216	212

Reasons for withdrawal

Reasons for withdrawal
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Overall Study Death	99	84
Overall Study Withdrawal by Subject	23	29
Overall Study Physician Decision	16	5
Overall Study Lost to Follow-up	8	15
Overall Study Study terminated by Sponsor	70	79

Baseline Characteristics

Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Total n=447 Participants Total of all reporting groups
Age, Customized Years	70 Years n=5 Participants	69 Years n=7 Participants	69 Years n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	79 Participants n=7 Participants	165 Participants n=5 Participants
Sex: Female, Male Male	140 Participants n=5 Participants	142 Participants n=7 Participants	282 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Mixed Race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	201 Participants n=5 Participants	196 Participants n=7 Participants	397 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months

Population: Intent-to-Treat (ITT) Population: all par. randomized to study treatment regardless of whether or not they received treatment. PFS was assessed by a blinded independent review committee according to the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines.

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC)	13.1 Months Interval 10.6 to 13.8	22.4 Months Interval 19.0 to 25.2

SECONDARY outcome

Timeframe: From randomization until the 259th PFS event occurred, up to about 49 months

Population: ITT population. Only those participants with data available at the indicated time points were analyzed. OR was according to the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines. The 95% exact binomial confidence interval is for CR+CRi+nPR+PR.

OR is defined as the number of participants achieving an objective response (complete response \[CR\], CR with incomplete bone marrow recovery \[CRi\], partial response \[PR\], and nodular PR \[nPR\]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With the Best Overall Response (OR), as Assessed by the IRC CR	3 Participants	27 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the IRC CRi	0 Participants	5 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the IRC nPR	0 Participants	1 Participants
Number of Participants With the Best Overall Response (OR), as Assessed by the IRC PR	152 Participants	149 Participants

SECONDARY outcome

Timeframe: From randomization until the 259th PFS event occurred (Median follow-up approximately 28.9 months)

Population: ITT population. Only those participants with data available at the indicated time points were analyzed.

MRD was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) MRD negative, irrespective of response	8 Participants	26 Participants
Number of Participants Who Were Negative for Minimal Residual Disease (MRD) MRD negative, with an IRC-assessed CR	0 Participants	10 Participants

SECONDARY outcome

Timeframe: From randomization up to about 111 months

Population: ITT population. Only those participants with data available at the indicated time points were analyzed.

Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the total IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Overall Survival	84.67 Months Interval 74.25 to the upper limit of the confidence interval was not estimable due to insufficient number of patients with events.	NA Months Interval 84.5 to the median/upper limit of the confidence interval was not estimable due to insufficient number of patients with events.

SECONDARY outcome

Timeframe: From randomization uo to about 27 months

Population: ITT population. Time to response was measured using the International Workshop for CLL (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines 2008.

Time to response is defined as the time from randomization to the first response (CR, CRi, nPR, or PR). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) \> 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils \>1500 per microliter (µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11 grams/deciliter (g/dL), lymphocytes (LC) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL \>100,000/µL or 50% improvement over Baseline (BL), Hb \>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. Participants with unknown or missing responses were considered as non-responders. Only responders (CR, CRi, PR, nPR) were included in the analysis.

Outcome measures

Outcome measures
Measure	Chlorambucil n=154 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=182 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Time to Response, as Assessed by the IRC	1.9 Months Interval 1.2 to 1.9	1.2 Months Interval 1.0 to 1.9

SECONDARY outcome

Timeframe: From randomization up to about 43 months

Population: ITT population. Only those participants with data available at the indicated time points were analyzed. Only responders (CR, CRi, PR, nPR) were included in the analysis.

DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time (\>= 12 weeks) were censored at the date of the last visit with adequate assessment. Par. with unknown or missing responses were considered as non-responders.

Outcome measures

Outcome measures
Measure	Chlorambucil n=154 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=182 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Duration of Response (DOR), as Assessed by the IRC	13.2 Months Interval 10.8 to 16.4	22.1 Months Interval 19.1 to 24.6

SECONDARY outcome

Timeframe: From randomization up to about 49 months

Population: ITT population. Only those participants with data available at the indicated time points were analyzed.

Time to progression is defined as the time from the date of randomization to disease progression (PD). PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Participants who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time were censored at the date of the last visit with adequate assessment.

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Time to Progression, as Assessed by the IRC	13.6 Months Interval 11.2 to 14.6	23.1 Months Interval 21.2 to 25.8

SECONDARY outcome

Timeframe: From randomization up to about 49 months

Population: ITT population. Only those participants with data available at the indicated time points were analyzed.

Time to next therapy is defined as the time from randomization until the start of the next-line of treatment.

Outcome measures

Outcome measures
Measure	Chlorambucil n=99 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=64 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Time to Next Therapy	24.67 Months Interval 22.57 to 29.08	39.82 Months Interval 34.69 to 48.79

SECONDARY outcome

Timeframe: Baseline, Cycle 3 Day 1, 1 month Follow-up

Population: ITT population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead. Participants with an ECOG performance status of 0 or 1 are shown..

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With Improvement in ECOG Performance Status of 0 or 1 ECOG (0, 1) at Baseline	209 Participants	200 Participants
Number of Participants With Improvement in ECOG Performance Status of 0 or 1 ECOG (0, 1) at Cycle 3 Day 1	184 Participants	189 Participants
Number of Participants With Improvement in ECOG Performance Status of 0 or 1 ECOG (0, 1) 1 Month Follow-up	183 Participants	191 Participants

SECONDARY outcome

Timeframe: Baseline, Cycle 3 Day 1, and 1 month Follow-up

Assessment for the presence of the following symptoms were performed at Screening, Day 1 of each treatment cycle and at every Follow-up visit: night sweats (without signs of infection); unexplained, unintentional weight loss \>= 10% within the previous 6 months; recurrent, unexplained fever of greater than 38 degrees celsius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue. The best response refers to overall best response in terms of CR, CRi, PR or nPR. Data are presented for constitutional response= yes and no.

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With Improvement in Constitutional Symptoms (CS) CS present, Baseline, n=226, 221	120 Participants	118 Participants
Number of Participants With Improvement in Constitutional Symptoms (CS) CS present, Cycle 3 Day 1, n=198, 199	44 Participants	33 Participants
Number of Participants With Improvement in Constitutional Symptoms (CS) CS present, 1 Month Follow-up, n=198, 200	23 Participants	22 Participants

SECONDARY outcome

Timeframe: Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up

Population: Safety population: all participants who received at least 1 dose of a study drug. Only participants with post-ofatumumab HAHA Results are included.

Serum samples for analysis of HAHA were collected at Baseline (Screening), Cycle 4 Day 1 (after 3 months of treatment), and at 1 month and 6 months post last dose of ofatumumab. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive and further evaluated in the titration test to obtain a titer of HAHA.

Outcome measures

Outcome measures
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result	—	0 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1,Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, and Cycle 9 Day 1

Population: Pharmacokinetic (PK) Population: all participants for whom a pharmacokinetic sample was obtained and analyzed.

Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of treatment.

Outcome measures

Outcome measures
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=193 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Cmax and Ctrough of Ofatumumab Cmax, Cycle 1 Day 1, n=0, 176	—	51.8 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 1.03
Cmax and Ctrough of Ofatumumab Cmax, Cycle 1 Day 8, n=0, 193	—	241 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 0.46
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 1 Day 8, n=0, 99	—	2.5 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 5.85
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 2 Day 1, n=0, 138	—	5.2 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 15.37
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 3 Day 1, n=0, 142	—	6.2 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 17.06
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 4 Day 1, n=0, 147	—	15.5 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 7.99
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 5 Day 1, n=0, 149	—	33.5 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 3.61
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 6 Day 1, n=0, 155	—	45.9 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 2.77
Cmax and Ctrough of Ofatumumab Ctrough, Cycle 9 Day 1, n=0, 56	—	55.6 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 3.50
Cmax and Ctrough of Ofatumumab Cmax, Cycle 4 Day 1, n=0, 169	—	285 Micrograms/Milliliter (µg/mL) Geometric Coefficient of Variation 0.44

SECONDARY outcome

Timeframe: Cycle 4 Day 1

Population: PK Population.

Plasma clearance is defined as the plasma volume which is totally cleared of drug per unit of time. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Outcome measures

Outcome measures
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=183 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Total Plasma Clearance (CL) of Ofatumumab	—	15.4 Milliliter/hour (mL/h) Geometric Coefficient of Variation 0.73

SECONDARY outcome

Timeframe: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1

Population: PK Population. Only those participants available at the indicated time points were assessed. The number of participants assessed at each time point is indicated by "n=X,X.

Area under the concentration time curve over the dosing interval \[AUC(0-tau)\] is a measure of drug exposure over time. AUC(0-tau) is defined as the area under the ofatumumab plasma concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of ofatumumab. For estimation of AUC(0-tau), blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hous after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Outcome measures

Outcome measures
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=208 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
AUC(0-tau) of Ofatumumab Cycle 1 Day 1, n=0, 193	—	2621 µg x hours/mL Geometric Coefficient of Variation 0.76
AUC(0-tau) of Ofatumumab Cycle 4 Day 1, n=0, 183	—	65100 µg x hours/mL Geometric Coefficient of Variation 0.73
AUC(0-tau) of Ofatumumab Cycle 1 Day 8, n=0, 208	—	25369 µg x hours/mL Geometric Coefficient of Variation 0.87

SECONDARY outcome

Timeframe: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1

Population: PK Population. Only those participants available at the indicated time points were assessed. The number of participants assessed at each time point is indicated by "n=X,X.

Volume of distribution at steady state (Vss) is defined as the distribution of a drug between plasma and the rest of the body at steady state. Blood samples were collected from participants who received ofatumumab plus chlorambucil at predose and 0.5 hour after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Outcome measures

Outcome measures
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=208 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Volume of Distribution at Steady State (Vss) of Ofatumumab Vss, Cycle 1 Day 1, n=0, 193	—	7.78 Liters Geometric Coefficient of Variation 0.55
Volume of Distribution at Steady State (Vss) of Ofatumumab Vss, Cycle 1 Day 8, n=0, 208	—	7.77 Liters Geometric Coefficient of Variation 0.54
Volume of Distribution at Steady State (Vss) of Ofatumumab Vss, Cycle 4 Day 1, n=0, 183	—	8.06 Liters Geometric Coefficient of Variation 0.53

SECONDARY outcome

Timeframe: Cycle 4 Day 1

Population: PK Population

The terminal half-life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original concentration. Blood samples were collected to assess the plasma half-life of ofatumumab. Blood samples were collected from participants who received ofatumumab plus chlorambucil pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Outcome measures

Outcome measures
Measure	Chlorambucil Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=183 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Plasma Half Life (t1/2) of Ofatumumab	—	445 hours Geometric Coefficient of Variation 1.05

SECONDARY outcome

Timeframe: Cycle 3 Day 1

Population: Chlorambucil/PAAM pharmacokinetic (PK) Population (substudy): all participants for whom a chlorambucil/PAAM sample is obtained and analyzed.

Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The maximum observed concentration (Cmax) of chlorambucil and PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) \[No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00\].

Outcome measures

Outcome measures
Measure	Chlorambucil n=7 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=12 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM) Chlorambucil Cmax/Dose	27.1 nanograms per milliliter per milligram Standard Deviation 0.32	38.4 nanograms per milliliter per milligram Standard Deviation 0.36
Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM) PAAM Cmax/Dose	19.3 nanograms per milliliter per milligram Standard Deviation 0.23	24.3 nanograms per milliliter per milligram Standard Deviation 0.30

SECONDARY outcome

Timeframe: Cycle 3 Day 1

Population: Chlorambucil/PAAM pharmacokinetic (PK) Population (substudy): all participants for whom a chlorambucil/PAAM sample is obtained and analyzed.

Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-inf\]) and over 6 hours (AUC\[0-6\]) of chlorambucil and AUC(0-6) of PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) \[No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00\].

Outcome measures

Outcome measures
Measure	Chlorambucil n=7 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=12 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM) Chlorambucil AUC(0-6)/Dose	67.84 Hours*nanogram/milliliter/milligram Standard Deviation 0.24	65.43 Hours*nanogram/milliliter/milligram Standard Deviation 0.44
Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM) Chlorambucil AUC(0-inf)/Dose	74.42 Hours*nanogram/milliliter/milligram Standard Deviation 0.23	67.10 Hours*nanogram/milliliter/milligram Standard Deviation 0.45
Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM) PAAM AUC(0-6)/Dose	71.52 Hours*nanogram/milliliter/milligram Standard Deviation 0.26	80.32 Hours*nanogram/milliliter/milligram Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline, Cycle 4 day 1, cycle 7 day 1, 1 month follow-up, 6 month follow-up, 12 month follow-up

HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQC30), Chronic Lymphocytic Leukemia module (EORTC QLQ-CLL16), EuorQoL-Five Dimension (EQ-5D), and HCQ. Period (P)1 (Day 85, Day 169, Day 253) and P2 (scheduled follow-up (FU) and withdrawal visits) analysis were considered. Baseline (BL) for P1 was defined as score from screening visit and BL for P2 was defined as the last on-treatment score. The 2 principal QoL outcomes were pre-specified as the Global Health scale (GHS/QOL) of the EORTC QLQ-C30 and fatigue scale of the EORTC QLQ-CLL16. For EORTC QLQ-C30,GHS/Qol, the possible scale range was 0-100 (with 100 being 'best') and a positive difference from BL is indicative of better functioning (range -100 to +100). For the EORTC QLQ-CLL16 fatigue scale, the possible scale range was 0-100 (with 0 being 'best') and a negative difference from BL represents an improvement in fatigue (range -100 to +100).

Outcome measures

Outcome measures
Measure	Chlorambucil n=226 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Change From Baseline in Health Related Quality of Life (HRQOL) P1,Cycle 4 Day 1,QLQCLL16 fatigue score, n=145,163	-4.71 Scores on a scale Standard Deviation 27.48	-4.60 Scores on a scale Standard Deviation 24.23
Change From Baseline in Health Related Quality of Life (HRQOL) P1, Cycle 7 Day 1,QLQCLL16 fatigue score, n=55,57	-1.21 Scores on a scale Standard Deviation 25.43	-9.36 Scores on a scale Standard Deviation 22.93
Change From Baseline in Health Related Quality of Life (HRQOL) P2,1 month FU, QLQC30 GHS/QoL score, n=118, 150	4.79 Scores on a scale Standard Deviation 23.13	0.56 Scores on a scale Standard Deviation 18.31
Change From Baseline in Health Related Quality of Life (HRQOL) P2, 6 month FU, QLQC30 GHS/QoL score, n=83, 129	3.01 Scores on a scale Standard Deviation 22.07	3.75 Scores on a scale Standard Deviation 20.83
Change From Baseline in Health Related Quality of Life (HRQOL) P2, 12 month FU, QLQC30 GHS/QoL score, n=48, 96	3.82 Scores on a scale Standard Deviation 18.27	1.22 Scores on a scale Standard Deviation 17.69
Change From Baseline in Health Related Quality of Life (HRQOL) P2, 1 month FU, QLQCLL16 fatigue score, n=121, 152	-1.24 Scores on a scale Standard Deviation 21.75	-0.33 Scores on a scale Standard Deviation 19.13
Change From Baseline in Health Related Quality of Life (HRQOL) P2, 6 month FU, QLQCLL16 fatigue score, n=85, 131	-7.06 Scores on a scale Standard Deviation 18.96	-2.93 Scores on a scale Standard Deviation 19.34
Change From Baseline in Health Related Quality of Life (HRQOL) P2, 12 month FU, QLQCLL16 fatigue score, n=51, 95	-2.94 Scores on a scale Standard Deviation 17.86	0.88 Scores on a scale Standard Deviation 16.91
Change From Baseline in Health Related Quality of Life (HRQOL) P1, Cycle 4 Day 1, QLQC30 GHS/QoL score, n=139,159	1.92 Scores on a scale Standard Deviation 21.22	6.08 Scores on a scale Standard Deviation 21.08
Change From Baseline in Health Related Quality of Life (HRQOL) P1, Cycle 7 Day 1, QLQC30 GHS/QoL score, n=52, 55	8.01 Scores on a scale Standard Deviation 22.20	6.97 Scores on a scale Standard Deviation 17.55

SECONDARY outcome

Timeframe: From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months.

Population: Safety Population

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any AE	205 Participants	208 Participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any SAE	84 Participants	97 Participants

SECONDARY outcome

Population: Safety Population

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher Any AE, Grade 3	54 Participants	67 Participants
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher Any AE, Grade 4	31 Participants	36 Participants
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher Any AE, Grade 5	25 Participants	36 Participants
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher Any SAE, Grade 3	36 Participants	34 Participants
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher Any SAE, Grade 4	13 Participants	19 Participants
Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher Any SAE, Grade 5	25 Participants	36 Participants

SECONDARY outcome

Population: Safety Population

Participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented by treatment cycle. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)	92 Participants	83 Participants

SECONDARY outcome

Population: Safety Population

AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease	6 Participants	4 Participants

SECONDARY outcome

Timeframe: From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 28.9 months)

Population: Safety Population

Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products are counted in this table.

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=217 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study No transfusions	159 Participants	168 Participants
Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study At least one transfusion	68 Participants	49 Participants

SECONDARY outcome

Timeframe: From start of treatment up to 30 days after last treatment

Population: Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.

Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Chlorambucil n=227 Participants Participants with previously untreated chronic lymphocytic leukemia (CLL) received chlorambucil monotherapy 10 milligram (mg)/meter squared (m\^2) orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.	Ofatumumab + Chlorambucil n=221 Participants Participants with CLL received intravenous (IV) infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by IV infusions of 1000 mg on the first day of each subsequent 28-day cycle in combination with chlorambucil 10 mg/m\^2 orally on Days 1-7 of every 28-day cycle for a minimum of 3 cycles until best response or a maximum of 12 cycles.
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM IgA, n=175, 186	0.047 Gram per liter Standard Deviation 0.5706	0.048 Gram per liter Standard Deviation 0.4257
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM IgG, n=175, 186	-0.458 Gram per liter Standard Deviation 3.6177	-0.268 Gram per liter Standard Deviation 2.5430
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM IgM n=175, 186	-0.398 Gram per liter Standard Deviation 4.7864	-0.031 Gram per liter Standard Deviation 0.2507

Adverse Events

Chlorambucil

Serious events: 57 serious events

Other events: 175 other events

Deaths: 99 deaths

Ofatumumab 1000 mg + Chlorambucil

Serious events: 53 serious events

Other events: 183 other events

Deaths: 84 deaths

Total

Serious events: 110 serious events

Other events: 358 other events

Deaths: 183 deaths

Serious adverse events

Other adverse events

Additional Information

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Results disclosure agreements

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