A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01563055
• Collaborator: (none)
• Enrollment: 10
• Locations: 6
• Arm: 1
• Duration (Months): 31
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label study to evaluate tolerability, safety, efficacy and pharmacokinetic profile of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated Chronic Lymphocytic Leukemia (CLL).

Condition or Disease	Intervention/Treatment	Phase
Leukaemia, Lymphocytic, Chronic	Drug: chlorambucil, tablets; Drug: ofatumumab (GSK1841157) infusion	Phase 2

Detailed Description

This is an open-label study to evaluate tolerability, safety, efficacy and pharmacokinetic profile of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated Chronic Lymphocytic Leukemia (CLL). Ofatumumab will be infused intravenously at Day 1 (300 mg) and Day 8 (1000 mg) in the first 28-day cycle, followed by infusions of 1000 mg at the first day of each 28-day cycle. Chlorambucil will be given 10 mg/m2 at Day 1-7 in each 28-day cycle.

The primary objectives are to evaluate tolerability and overall response rate (ORR) of ofatumumab with chlorambucil for previously untreated (frontline) CLL.

Secondary objectives include to evaluate complete remission (CR) rate, progression free survival (PFS), overall survival (OS), time to response, duration of response, time to next therapy, incidence and severity of adverse events and serious adverse events, incidences of grade 3 and 4 infections and myelosuppression (anemia, neutropenia, thrombocytopenia), and pharmacokinetics of ofatumumab and chlorambucil.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ofatumumab + chlorambucil ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles	Drug: chlorambucil, tablets; 2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles; Drug: ofatumumab (GSK1841157) infusion; iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Developed Toxicity Requiring Discontinuation From Study Treatment During Cycle 1 [From start of treatment through Cycle 1 (Week 4)]

   Tolerability of ofatumumab in combination with chlorambucil was evaluated based on the number of participants who developed toxicity requiring discontinuation from study treatment during Cycle 1. The treatment was considered tolerable when 0 of 3 participants, or <=2 of 6 participants developed toxicity which required discontinuation of study treatment during Cycle 1. The toxicity requiring discontinuation was determined based on the pre-defined withdrawal criteria.

2. Number of Participants With Overall Response, as Assessed by the Independent Review Committee (IRC) With CT, IRC and Investigator [From start of treatment until disease progression or death (up to Week 62.3)]

   Response evaluated as per International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-sponsored Working Group (NCI-WG) Guidelines, 2008. Overall response rate (ORR) is defined as percentage of par. achieving complete remission (CR), nodular partial remission (nPR), CR-incomplete (CRi) or PR. CR (>=2 months after last treatment): lymphocytes (LC) <4000 per microliter (μL), no lymphadenopathy (Ly)>1.5 cm/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils (N)>1500/µL, platelets (PL)>100,000/µL, hemoglobin (Hb)>11 grams/deciliter (g/dL), bone marrow (BM) sample must be normocellular for age,<30% LC, no lymphoid nodule (LN). PR:>=50% decrease in LC, Ly, size of liver and spleen; and at least one of these: N>1500/μL, PL>100,000/µL or 50% improvement over Baseline (BL), Hb>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.

Secondary Outcome Measures

1. Number of Participants With CR, as Assessed by the IRC, IRC With CT, and the Investigator [From start of treatment until disease progression or death (up to Week 62.3)]

   Response was determined according to the IWCLL updated NCI-WG guidelines, 2008. According to the guidelines, CR (all the criteria at least 2 months after last treatment): peripheral blood lymphocytes below < 4,000/μL, no Ly > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; Neu >1500 /µL, PL >100,000/µL, Hb >11 g/dL, BM sample must be normocellular for age, <30% lymphocytes, no LN. PR: >=50% decrease in peripheral blood lymphocytes, Ly, size of liver and spleen; and blood count showing at least one of the following results: Neu>1500/μL, PL >100,000/µL or 50% improvement over BL, Hb >11 g/dL or 50% improvement over BL. No increase in LN and no new LN.

2. Progression-free Survival (PFS), as Assessed by the IRC and the Investigator [From start of treatment until disease progression or death (up to Week 62.3)]

   Progression free survival is defined as the time from start of treatment until disease progression (PD) or death due to any cause. PD was determined by the IRC or investigator according to the definitions of response in the IWCLL updated NCI-WG guidelines, 2008. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [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 per microliter B-lymphocytes; transformation to a more aggressive histology; or occurrence of cytopenia attributable to chronic lymphocytic leukemia. PFS was censored at the last visit with adequate assessment for participants who were alive and had not progressed.

3. Overall Survival [From start of treatment until death (up to Week 62.3]

   Overall survival is defined as time from start of treatment until death due to any cause. For participants who did not die, time to death was censored at the time of the last date of contact.

4. Time to Response, as Assessed by the IRC [From start of treatment until the first response (CR/CRi/nPR/PR) (up to Week 62.3)]

   Time to response is defined as the time from start of treatment until the first response (CR/CRi/nPR/PR). Response was determined according to the IWCLL updated NCI-WG guidelines, 2008. This analysis only included participants who had a response while in the study, there was no censoring.

5. Duration of Response, as Assessed by the IRC [From initial response (CR/CRi/nPR/PR) until disease progression or death (up to Week 62.3)]

   Duration of response is defined as the time from the first documented evidence of CR, CRi, nPR or PR until the first documented sign of PD or death in participants with CR, CRi, nPR or PR. For participants who did not progress or die, duration of response was censored on the date of last assessment.

6. Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy [From start of treatment until the first administration of the next CLL therapy (up to Week 62.3)]

   Time to next CLL therapy is defined as the time from start of treatment until the first administration of the next CLL treatment other than chlorambucil administrations scheduled in this study. Time to next CLL therapy was restricted to the subgroup of the population who receive a next CLL therapy after experiencing disease progression.

7. Number of Participants With no B-symptoms (Constitutional Symptoms) and With at Least One B-symptom (Constitutional Symptoms) at the Indicated Time Points [Baseline, C2-D29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9 -D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)]

   The number of participants with no B-symptoms (no night sweat [without signs of infection], no unexplained, unintentional weight loss >= 10% within the previous 6 months, no recurrent, unexplained fever of greater than 38 degrees celcius for 2 weeks and no extreme fatigue) and the number of participants with at least one of the B-symptoms are summarized by assessment time. The presence of the B-symptoms was assessed at Baseline, Day 1 of each treatment cycle and follow-up (FU). Baseline was the last pre-dose assessment performed at Cycle (C) 1-Day (D) 1.

8. Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Baseline, C2-D29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9 -D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)]

   ECOG PS is a scale to assess disease progression, extent to which disease affects the daily living abilities and determines appropriate treatment and prognosis. It is scored on a scale of 0 to 5 as, 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2 (ambulatory and capable of all self cares but unable to carry out any work activities, up and about > 50% of waking hours), 3 (capable of only limited self cares, confined to bed or chair > 50% of waking hours), 4 (completely disabled, cannot carry on any self cares, totally confined to bed or chair), 5 (death). Improvement is defined as decrease from Baseline by at least one step on the ECOG performance status scale (yes/no). Baseline was the last pre-dose assessment performed on Cycle 1-Day 1(C1-D1). When C1-D1 was missing, the last assessment performed prior to pre-dose C1-D1 was used. It was performed on Day 1 of each cycle and follow-up (FU).

9. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [From start of treatment until follow-up for survival (up to Week 62.3)]

   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 important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed.

10. Number of Participants With AEs of Maximum Severity [From start of treatment until follow-up for survival (up to Week 62.3)]

    Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.03 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death). AEs not in the list of CTCAE were graded at discretion of the investigator.

11. Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events [From start of treatment until follow-up for survival (up to Week 62.3)]

    Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.03 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death). AEs not in the list of CTCAE were graded at discretion of the investigator. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Participants with Grade (G)3 or G4 adverse event of infection and myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Also presented are number of participants with autoimmune hemolytic anemia (AIHA). 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.

12. Number of Participants With the Indicated Results for Human Anti-human Antibody (HAHA) at the Indicated Time Points [Screening, Cycle 4-Day 85, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), and FU 169-PDFU 169 (168 days after FU-1)]

    HAHA are indicators of immunogenicity induced by ofatumumab. Blood samples were taken from participants at Screening, Cycle 4-Day 85, FU 1-PDFU 1, and FU 169-PDFU 169. The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. The results are presented as participants with HAHA results as positive, negative or confirmation required.

13. Mean Change From Baseline in the Immunoglobulins (Ig) Antibodies IgA, IgG, and IgM at the Indicated Time Points [Baseline (Cycle 1-Day 1), FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), and FU 169-PDFU 169 (168 days after FU-1)]

    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. Immunoglobulins were measured at Cycle 1-Day 1, FU 1-PDFU 1, and FU 169-PDFU 169 for participants in CR, PR, and stable disease (SD).

14. Number of Participants Who Were Positive or Negative for Minimal Residual Disease (MRD), as Assessed by IRC With CT [FU 85-PDFU 85 (84 days after FU-1)]

    MRD refers to small number of leukemic cells that remain in the participant's body during treatment or after treatment in participants who achieved a confirmed complete remission. MRD assessment in bone marrow aspiration sample was perfrmed by flow cytometry (cluster of differentiation [CD]5, CD19, CD20, CD23). The absence of MRD was defined as less than one CLL cell per 10,000 leukocytes. The number of participants who were positive and negative for MRD are presented.

15. Change From Baseline in CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points [Baseline, C1-D15, C2-D29, C2-D43, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9-D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)]

    CD5+CD19+ cells were counted in peripheral blood by flow cytometry. Baseline CD5+CD19+ and CD5-CD19+ cell count value is 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. B-cell monitoring (CD5+CD19+ and CD5-CD19+) was performed at Cycle 1 (Day 1, Day 15) and Cycle 2 (Day 29, Day 43), on Day 1 of Cycle 3, 4, 5, 6, 9 and 12 (Day 57, Day 85, Day 113, Day 141, Day 225, Day 309), 28 days after the first day of the last treatment cycle (FU 1-PDFU 1) for all participants depending on the number of cycles administered, and 84 and 168 days after the day of FU 1-PDFU 1 for participants in CR, PR, and SD.

16. Beta-2 Microglobulin at Cycle 1-Day 1 [Cycle 1-Day 1]

    Beta-2-microglobulin is a protein present on the surface of most cells. Higher levels indicate a poor prognosis of CLL. Beta-2 microglobulin was measured at Cycle 1-Day 1.

17. Complement (CH50) at Cycle 1-Day 1 and Cycle 4-Day 85 [Cycle 1-Day 1 and Cycle 4-Day 85]

    The CH50 is the serum complement to lyse 50% of sensitized red blood cells; it is a marker of complement activation. A high CH50 level suggests evidence for complement activation, whereas a low CH50 level suggests lack of complement activation. Peripheral blood samples were collected for analysis at Cycle 1-Day 1 and Cycle 4-Day 85.

18. Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab [Cycle 1-Day 1 and Cycle 3-Day 57]

    Maximum (peak) plasma drug concentration of ofatumumab was determined at Cycle 1-Day 1 and Cycle 3-Day 57. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr), and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

19. Cmax of Serum Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Cmax of serum chlorambucil was assesed at Cycle 1-Day 1, Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

20. Cmax of Serum Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Cmax of chlorambucil metabolite phenyl acetic acid mustard was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

21. Minimum Plasma Concentration (Cmin) of Ofatumumab [Cycle 1-Day 8, Cycle 2-Day 29, Cycle 3-Day 57, Cycle 4-Day 85, Cycle 5-Day 113, and Cycle 6-Day 141]

    Minimum plasma drug concentration of ofatumumab was determined at Cycle 1-Day 8, Cycle 2-Day 29, Cycle 3-Day 57, Cycle 4-Day 85, Cycle 5-Day 113, and Cycle 6-Day 141. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr), Cycle 2-Day 29 (pre-dose), Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr), Cycle 4-Day 85 (pre-dose, 30 min post end of infusion), Cycle 5-Day 113 (pre-dose and end of infusion) and Cycle 6-Day 141 (pre-dose and end of infusion).

22. Cmin of Chlorambucil [Cycle 1-Day 4 and Cycle 3-Day 57]

    Cmin of chlorambucil was assesed at Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

23. Cmin of Phenyl Acetic Acid Mustard [Cycle 1-Day 4 and Cycle 3-Day 57]

    Cmin of chlorambucil metabolite phenyl acetic acid mustard was assesed at Cycle 1-Day 4 and Cycle 3-Day 57. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

24. Total Plasma Clearance (CL) of Ofatumumab [Cycle 1-Day 1]

    Plasma clearance is defined as the plasma volume which is totally cleared of drug per unit of time. Blood samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

25. Area Under the Drug Plasma Concentration-time Curve From Dosing to Time Tau (AUC[0-tau]) of Ofatumumab [Cycle 1-Day 1 and Cycle 3-Day 57]

    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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. For ofatumumab it was assesed at Cycle 1-Day 1 and Cycle 3-Day 57. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

26. AUC(0-tau) of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

27. AUC(0-tau) of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

28. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab [Cycle 1-Day 1]

    The total AUC or AUC0-infinity is the area under the curve from time 0 extrapolated to infinite time. It was assesed on Cycle 1-Day 1. The samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

29. AUC(0-infinity) for Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    The total AUC or AUC0-infinity is the area under the curve from time 0 extrapolated to infinite time. It was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

30. AUC(0-infinity) for Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    The total AUC or AUC(0-infinity) is the area under the curve from time 0 extrapolated to infinite time. It was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

31. Volume of Distribution at Steady State (Vss) of Ofatumumab [Cycle 1-Day 1]

    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. Samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

32. Plasma Half-life (t1/2) of Ofatumumab [Cycle 1-Day 1 and Cycle 3-Day 57]

    t1/2 is the time required for the plasma concentration of ofatumumab to decrease by half. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

33. Plasma Half-life (t1/2) of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    t1/2 is the time required for the serum concentration of chlorambucil to decrease by half. Blood samples for serum concentration of chlorambucil was collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

34. Plasma Half-life (t1/2) of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    t1/2 is the time required for the plasma/serum concentration of phenylacetic acid mustard to decrease by half. Blood samples for serum concentration of phenylacetic acid mustard was collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

35. Time to Maximum Concentration (Tmax) of Ofatumumab [Cycle 1-Day 1 and Cycle 3-Day 57]

    Tmax is the time required for reaching maximum concentration of drug (Cmax). Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).

36. Time to Maximum Concentration (Tmax) of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Tmax is the time required for reaching maximum concentration of drug (Cmax). Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

37. Time to Maximum Concentration (Tmax) of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Tmax is the time required for reaching maximum concentration of drug (Cmax). Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

38. Mean Residence Time to Infinity (MRTinf) of Ofatumumab [Cycle 1-Day 1]

    MRTinf is the average amount of time that ofatumumab spends in the body. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

39. Mean Residence Time Inf (MRTinf) of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    MRTinf is the average amount of time that chlorambucil spends in the body. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

40. Mean Residence Time Inf (MRTinf) of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    MRTinf is the average amount of time that phenyl acetic acid mustard spends in the body. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

41. Volume of Distribution (Vz) of Ofatumumab [Cycle 1-Day 1]

    Vz for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body during the terminal phase to the plasma concentration during the terminal phase. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).

42. Apparent Total Clearance of the Drug From Plasma (CL/F) for Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    CL/F is defined as the apparent total clearance of the drug from plasma after oral administration of chlorambucil. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

43. Apparent Volume of Distribution During Terminal Phase (Vz/F) of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Vz/F of chlorambucil is defined as the apparent volume of distribution during terminal phase after non-intravenous (oral) administration of chlorambucil. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

44. %AUC_extrap of Ofatumumab [Cycle 1-Day 1]

    %AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr).

45. %AUC_extrap of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    %AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

46. %AUC_extrap of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    %AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

47. AUC (0-t) of Ofatumumab [Cycle 1-Day 1 and Cycle 3-Day 57]

    AUC (0-t) represents the area under the concentration curve of ofatumumab in plasma from 0 to time t hours. AUC (0-t) was assessed at 168 hours and 672 hours post-dose.

48. AUC (0-t) of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    AUC (0-t) represents the area under the concentration curve of chlorambucil in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.

49. AUC (0-t) of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    AUC (0-t) represents the area under the concentration curve of phenyl acetic acid mustard in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.

50. Dose Normalized Cmax (Cmax/D) for Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Cmax/D is defined as the maximum plasma concentration (Cmax) per unit dose. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

51. Cmax/D for Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Cmax/D is defined as the maximum plasma concentration (Cmax) per unit dose. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

52. AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D, and AUC (0-tau)/D of Chlorambucil [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Dose adjusted AUC for the indicated time points were assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

53. AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D and AUC (0-tau)/D of Phenyl Acetic Acid Mustard [Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57]

    Dose adjusted AUC for the indicated time points were assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of CLL defined by : Circulating B lymphocytes ≥5,000 /μL AND Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, and CD23 prior to Visit 2.

• Considered inappropriate for fludarabine-based therapy

• Active disease and indication for treatment based on modified NCI-WG guidelines defined by presenting at least any one of the following conditions :

Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia.

Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.

Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.

Progressive lymphocytosis with an increase of more than 50% over a two month period or an lymphocyte doubling time of less than 6 months.

A minimum of any one of the following disease-related symptoms must be present : a) Unintentional Weight loss ≥ 10% within the previous six months ; b) Fevers >38.0 degree C for ≥ 2 weeks without evidence of infection ; or c) Night sweats for more than 1 month without evidence of infection.

• Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment permitted).

• ECOG Performance Status of 0-2.

• Life expectancy of at least 6 months, in the opinion of the investigator.

• Age ≥ 20 years.

• Signed written informed consent prior to performing any study-specific procedures.

• Patients possible to stay at the trial site for at least two days (the day of the first infusion and a subsequent day).

Exclusion Criteria:

• Prior immuno- or chemotherapy for CLL or small lymphocytic lymphoma (SLL) with any agent except corticosteroids used to treat autoimmune hemolytic anemia.

• Previous autologous or allogeneic stem cell transplantation.

• Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100 mg/day equivalent to hydrocortisone, or chemotherapy.

• Known transformation of CLL (e.g. Richter).

• Known CNS involvement of CLL.

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.

• Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.

• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening (Visit 1), congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.

• History of significant cerebrovascular disease or event with significant symptoms or sequelae*.

• Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for <7 days for exacerbations other than CLL (e.g. asthma).

• Known HIV positive.

• Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb and/or HBsAb positive, an HBV DNA test will be performed and if positive the subject will be excluded.

• Screening laboratory values :

Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance). Total bilirubin > 2.0 times upper normal limit (unless due to Gilbert's syndrome).

Alanine transaminase (ALT) > 3.0 times upper normal limit.

• Previous treatment or known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor is a contraindication to their participation in the present study.

• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to Visit 1, whichever is longer, treatment with any anti-CD20 monoclonal antibody within 3 months of Visit 1, or participation in any other interventional clinical study. Note: Participation in any other interventional clinical study after disease progression during post PD-follow-up is permitted.

• Known or suspected inability to comply with study protocol.

• Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as oral hormonal birth control, intrauterine device, male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Aichi		Japan	466-8650
2	GSK Investigational Site	Hokkaido		Japan	060-8543
3	GSK Investigational Site	Kanagawa		Japan	259-1143
4	GSK Investigational Site	Kyoto		Japan	602-8566
5	GSK Investigational Site	Tokyo		Japan	104-0045
6	GSK Investigational Site	Tokyo		Japan	135-8550

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: NCT01563055
• Other Study ID Numbers: 115601
• First Posted: Mar 26, 2012
• Last Update Posted: Aug 10, 2015
• Last Verified: Jul 1, 2015

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Ofatumumab; Chlorambucil

Study Results

Participant Flow

Pre-assignment Detail	This study consisted of two parts. In part A of the study, the eligible participants (par.) were enrolled to assess the tolerability of ofatumumab with chlorambucil. After confirmation of the tolerability, Part B of the study was initiated. The total number of participants in Part A and Part B was 10.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Overall Participants	10
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	71.5 (10.38)
Age, Customized (Number) [Number]
<65 years	1 10%
>=65 years	9 90%
>=75 years	4 40%
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Race/Ethnicity, Customized (Number) [Number]
Asian - Japanese Heritage	10 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Developed Toxicity Requiring Discontinuation From Study Treatment During Cycle 1
Description	Tolerability of ofatumumab in combination with chlorambucil was evaluated based on the number of participants who developed toxicity requiring discontinuation from study treatment during Cycle 1. The treatment was considered tolerable when 0 of 3 participants, or <=2 of 6 participants developed toxicity which required discontinuation of study treatment during Cycle 1. The toxicity requiring discontinuation was determined based on the pre-defined withdrawal criteria.
Time Frame	From start of treatment through Cycle 1 (Week 4)

Outcome Measure Data

Analysis Population Description

All Subjects Population: all participants who received at least one dose of investigational product.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	3
Number [Participants]	0 0%

2. Primary Outcome

Title	Number of Participants With Overall Response, as Assessed by the Independent Review Committee (IRC) With CT, IRC and Investigator
Description	Response evaluated as per International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-sponsored Working Group (NCI-WG) Guidelines, 2008. Overall response rate (ORR) is defined as percentage of par. achieving complete remission (CR), nodular partial remission (nPR), CR-incomplete (CRi) or PR. CR (>=2 months after last treatment): lymphocytes (LC) <4000 per microliter (μL), no lymphadenopathy (Ly)>1.5 cm/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils (N)>1500/µL, platelets (PL)>100,000/µL, hemoglobin (Hb)>11 grams/deciliter (g/dL), bone marrow (BM) sample must be normocellular for age,<30% LC, no lymphoid nodule (LN). PR:>=50% decrease in LC, Ly, size of liver and spleen; and at least one of these: N>1500/μL, PL>100,000/µL or 50% improvement over Baseline (BL), Hb>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.
Time Frame	From start of treatment until disease progression or death (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
IRC with CT Assessed, CR	0 0%
IRC with CT Assessed, CRi	0 0%
IRC with CT Assessed, nPR	0 0%
IRC with CT Assessed, PR	5 50%
IRC Assessed, CR	1 10%
IRC Assessed, CRi	0 0%
IRC Assessed, nPR	1 10%
IRC Assessed, PR	5 50%
Investigator Assessed, CR	1 10%
Investigator Assessed, CRi	0 0%
Investigator Assessed, nPR	0 0%
Investigator Assessed, PR	6 60%

3. Secondary Outcome

Title	Number of Participants With CR, as Assessed by the IRC, IRC With CT, and the Investigator
Description	Response was determined according to the IWCLL updated NCI-WG guidelines, 2008. According to the guidelines, CR (all the criteria at least 2 months after last treatment): peripheral blood lymphocytes below < 4,000/μL, no Ly > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; Neu >1500 /µL, PL >100,000/µL, Hb >11 g/dL, BM sample must be normocellular for age, <30% lymphocytes, no LN. PR: >=50% decrease in peripheral blood lymphocytes, Ly, size of liver and spleen; and blood count showing at least one of the following results: Neu>1500/μL, PL >100,000/µL or 50% improvement over BL, Hb >11 g/dL or 50% improvement over BL. No increase in LN and no new LN.
Time Frame	From start of treatment until disease progression or death (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
IRC with CT Assessed, CR	0 0%
IRC Assessed, CR	1 10%
Investigator Assessed, CR	1 10%

4. Secondary Outcome

Title	Progression-free Survival (PFS), as Assessed by the IRC and the Investigator
Description	Progression free survival is defined as the time from start of treatment until disease progression (PD) or death due to any cause. PD was determined by the IRC or investigator according to the definitions of response in the IWCLL updated NCI-WG guidelines, 2008. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [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 per microliter B-lymphocytes; transformation to a more aggressive histology; or occurrence of cytopenia attributable to chronic lymphocytic leukemia. PFS was censored at the last visit with adequate assessment for participants who were alive and had not progressed.
Time Frame	From start of treatment until disease progression or death (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only participants who progressed or died were analyzed.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
IRC Assessed, Response, n=1	NA
Investigator Assessed, Response, n=1	NA

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from start of treatment until death due to any cause. For participants who did not die, time to death was censored at the time of the last date of contact.
Time Frame	From start of treatment until death (up to Week 62.3

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Median (95% Confidence Interval) [Weeks]	NA

6. Secondary Outcome

Title	Time to Response, as Assessed by the IRC
Description	Time to response is defined as the time from start of treatment until the first response (CR/CRi/nPR/PR). Response was determined according to the IWCLL updated NCI-WG guidelines, 2008. This analysis only included participants who had a response while in the study, there was no censoring.
Time Frame	From start of treatment until the first response (CR/CRi/nPR/PR) (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants classified as responders (CR, CRi, PR, nPR) were evaluated.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	7
Median (95% Confidence Interval) [Weeks]	4.1

7. Secondary Outcome

Title	Duration of Response, as Assessed by the IRC
Description	Duration of response is defined as the time from the first documented evidence of CR, CRi, nPR or PR until the first documented sign of PD or death in participants with CR, CRi, nPR or PR. For participants who did not progress or die, duration of response was censored on the date of last assessment.
Time Frame	From initial response (CR/CRi/nPR/PR) until disease progression or death (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants classified as responders (CR, CRi, PR, nPR) were evaluated.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	7
Median (95% Confidence Interval) [Weeks]	NA

8. Secondary Outcome

Title	Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy
Description	Time to next CLL therapy is defined as the time from start of treatment until the first administration of the next CLL treatment other than chlorambucil administrations scheduled in this study. Time to next CLL therapy was restricted to the subgroup of the population who receive a next CLL therapy after experiencing disease progression.
Time Frame	From start of treatment until the first administration of the next CLL therapy (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants who received next CLL therapy were evaluated.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	1
Median (95% Confidence Interval) [Weeks]	11.4

9. Secondary Outcome

Title	Number of Participants With no B-symptoms (Constitutional Symptoms) and With at Least One B-symptom (Constitutional Symptoms) at the Indicated Time Points
Description	The number of participants with no B-symptoms (no night sweat [without signs of infection], no unexplained, unintentional weight loss >= 10% within the previous 6 months, no recurrent, unexplained fever of greater than 38 degrees celcius for 2 weeks and no extreme fatigue) and the number of participants with at least one of the B-symptoms are summarized by assessment time. The presence of the B-symptoms was assessed at Baseline, Day 1 of each treatment cycle and follow-up (FU). Baseline was the last pre-dose assessment performed at Cycle (C) 1-Day (D) 1.
Time Frame	Baseline, C2-D29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9 -D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Baseline, With no B-symptom, n=10	9 90%
Baseline, With at least one B-symptom, n=10	1 10%
Cycle 2-Day 29, With no B-symptom, n=8	8 80%
Cycle 2-Day 29, With at least one B-symptom, n=8	0 0%
Cycle 3-Day 57, With no B-symptom, n=8	8 80%
Cycle 3-Day 57, With at least one B-symptom, n=8	0 0%
Cycle 4-Day 85, With no B-symptom, n=7	7 70%
Cycle 4-Day 85, With at least one B-symptom, n=7	0 0%
Cycle 5-Day 113, With no B-symptom, n=7	7 70%
Cycle 5-Day 113, With at least one B-symptom, n=7	0 0%
Cycle 6-Day 141, With no B-symptom, n=7	7 70%
Cycle 6-Day 141, With at least one B-symptom, n=7	0 0%
Cycle 7-Day 169, With no B-symptom, n=2	2 20%
Cycle 7-Day 169, With at least one B-symptom, n=2	0 0%
Cycle 8-Day 197, With no B-symptom, n=2	2 20%
Cycle 8-Day 197, With at least one B-symptom, n=2	0 0%
Cycle 9-Day 225, With no B-symptom, n=2	2 20%
Cycle 9-Day 225, With at least one B-symptom, n=2	0 0%
FU 1-PDFU 1, With no B-symptom, n=9	9 90%
FU 1-PDFU 1, With at least one B-symptom, n=9	0 0%
FU 85-PDFU 85, With no B-symptom, n=9	9 90%
FU 85-PDFU 85, With at least one B-symptom, n=9	0 0%
FU 169-PDFU 169, With no B-symptom, n=8	8 80%
FU 169-PDFU 169, With at least one B-symptom, n=8	0 0%

10. Secondary Outcome

Title	Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Description	ECOG PS is a scale to assess disease progression, extent to which disease affects the daily living abilities and determines appropriate treatment and prognosis. It is scored on a scale of 0 to 5 as, 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2 (ambulatory and capable of all self cares but unable to carry out any work activities, up and about > 50% of waking hours), 3 (capable of only limited self cares, confined to bed or chair > 50% of waking hours), 4 (completely disabled, cannot carry on any self cares, totally confined to bed or chair), 5 (death). Improvement is defined as decrease from Baseline by at least one step on the ECOG performance status scale (yes/no). Baseline was the last pre-dose assessment performed on Cycle 1-Day 1(C1-D1). When C1-D1 was missing, the last assessment performed prior to pre-dose C1-D1 was used. It was performed on Day 1 of each cycle and follow-up (FU).
Time Frame	Baseline, C2-D29, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9 -D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Cycle 2-Day 29, Improved, n=8	0 0%
Cycle 2-Day 29, No change, n=8	8 80%
Cycle 2-Day 29, Deteriorated, n=8	0 0%
Cycle 3-Day 57, Improved, n=8	0 0%
Cycle 3-Day 57, No change, n=8	8 80%
Cycle 3-Day 57, Deteriorated, n=8	0 0%
Cycle 4-Day 85, Improved, n=7	0 0%
Cycle 4-Day 85, No change, n=7	7 70%
Cycle 4-Day 85, Deteriorated, n=7	0 0%
Cycle 5-Day 113, Improved, n=7	0 0%
Cycle 5-Day 113, No change, n=7	7 70%
Cycle 5-Day 113, Deteriorated, n=7	0 0%
Cycle 6-Day 141, Improved, n=7	0 0%
Cycle 6-Day 141, No change, n=7	6 60%
Cycle 6-Day 141, Deteriorated, n=7	1 10%
Cycle 7-Day 169, Improved, n=2	0 0%
Cycle 7-Day 169, No change, n=2	2 20%
Cycle 7-Day 169, Deteriorated, n=2	0 0%
Cycle 8-Day 197, Improved, n=2	0 0%
Cycle 8-Day 197, No change, n=2	2 20%
Cycle 8-Day 197, Deteriorated, n=2	0 0%
Cycle 9-Day 225, Improved, n=2	0 0%
Cycle 9-Day 225, No change, n=2	2 20%
Cycle 9-Day 225, Deteriorated, n=2	0 0%
FU 1-PDFU 1, Improved, n=9	0 0%
FU 1-PDFU 1, No change, n=9	9 90%
FU 1-PDFU 1, Deteriorated, n=9	0 0%
FU 85-PDFU 85, Improved, n=9	0 0%
FU 85-PDFU 85, No change, n=9	8 80%
FU 85-PDFU 85, Deteriorated, n=9	1 10%
FU 169-PDFU 169, Improved, n=8	0 0%
FU 169-PDFU 169, No change, n=8	8 80%
FU 169-PDFU 169, Deteriorated, n=8	0 0%

11. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Description	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 important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed.
Time Frame	From start of treatment until follow-up for survival (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Any AE	10 100%
Any SAE	2 20%

12. Secondary Outcome

Title	Number of Participants With AEs of Maximum Severity
Description	Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.03 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death). AEs not in the list of CTCAE were graded at discretion of the investigator.
Time Frame	From start of treatment until follow-up for survival (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Any AE Grade 1	0 0%
Any AE Grade 2	4 40%
Any AE Grade 3	5 50%
Any AE Grade 4	1 10%
Any AE Grade 5	0 0%

13. Secondary Outcome

Title	Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events
Description	Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.03 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death). AEs not in the list of CTCAE were graded at discretion of the investigator. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Participants with Grade (G)3 or G4 adverse event of infection and myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Also presented are number of participants with autoimmune hemolytic anemia (AIHA). 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.
Time Frame	From start of treatment until follow-up for survival (up to Week 62.3)

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Infections, G3	0 0%
Infections, G4	0 0%
Thrombocytopenia, G3	2 20%
Thrombocytopenia, G4	0 0%
Neutropenia, G3	2 20%
Neutropenia, G4	1 10%
Anemia, G3	0 0%
Anemia, G4	0 0%
Autoimmune Hematologic Complication	0 0%

14. Secondary Outcome

Title	Number of Participants With the Indicated Results for Human Anti-human Antibody (HAHA) at the Indicated Time Points
Description	HAHA are indicators of immunogenicity induced by ofatumumab. Blood samples were taken from participants at Screening, Cycle 4-Day 85, FU 1-PDFU 1, and FU 169-PDFU 169. The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. The results are presented as participants with HAHA results as positive, negative or confirmation required.
Time Frame	Screening, Cycle 4-Day 85, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), and FU 169-PDFU 169 (168 days after FU-1)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Screening, Positive, n=10	1 10%
Screening, Negative, n=10	9 90%
Screening, Confirmation required, n=10	0 0%
Cycle 4-Day 85, Positive, n=7	0 0%
Cycle 4-Day 85, Negative, n=7	7 70%
Cycle 4-Day 85, Confirmation required, n=7	0 0%
FU 1-PDFU 1, Positive, n=10	0 0%
FU 1-PDFU 1, Negative, n=10	10 100%
FU 1-PDFU 1, Confirmation required, n=10	0 0%
FU 169-PDFU 169, Positive, n=8	0 0%
FU 169-PDFU 169, Negative, n=8	8 80%
FU 169-PDFU 169, Confirmation required, n=8	0 0%

15. Secondary Outcome

Title	Mean Change From Baseline in the Immunoglobulins (Ig) Antibodies IgA, IgG, and IgM at the Indicated Time Points
Description	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. Immunoglobulins were measured at Cycle 1-Day 1, FU 1-PDFU 1, and FU 169-PDFU 169 for participants in CR, PR, and stable disease (SD).
Time Frame	Baseline (Cycle 1-Day 1), FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), and FU 169-PDFU 169 (168 days after FU-1)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
IgA, FU 1-PDFU 1, n=10	0.111 (0.2816)
IgA, FU 169-PDFU 169, n=8	0.326 (0.4172)
IgG, FU 1-PDFU 1, n=10	-0.025 (1.4555)
IgG, FU 169-PDFU 169, n=8	0.611 (1.0636)
IgM, FU 1-PDFU 1, n=10	-0.053 (0.1466)
IgM, FU 169-PDFU 169, n=8	-0.045 (0.1466)

16. Secondary Outcome

Title	Number of Participants Who Were Positive or Negative for Minimal Residual Disease (MRD), as Assessed by IRC With CT
Description	MRD refers to small number of leukemic cells that remain in the participant's body during treatment or after treatment in participants who achieved a confirmed complete remission. MRD assessment in bone marrow aspiration sample was perfrmed by flow cytometry (cluster of differentiation [CD]5, CD19, CD20, CD23). The absence of MRD was defined as less than one CLL cell per 10,000 leukocytes. The number of participants who were positive and negative for MRD are presented.
Time Frame	FU 85-PDFU 85 (84 days after FU-1)

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants who were positive and negative for MRD were analyzed.

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	8
Positive	4 40%
Negative	4 40%

17. Secondary Outcome

Title	Change From Baseline in CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points
Description	CD5+CD19+ cells were counted in peripheral blood by flow cytometry. Baseline CD5+CD19+ and CD5-CD19+ cell count value is 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. B-cell monitoring (CD5+CD19+ and CD5-CD19+) was performed at Cycle 1 (Day 1, Day 15) and Cycle 2 (Day 29, Day 43), on Day 1 of Cycle 3, 4, 5, 6, 9 and 12 (Day 57, Day 85, Day 113, Day 141, Day 225, Day 309), 28 days after the first day of the last treatment cycle (FU 1-PDFU 1) for all participants depending on the number of cycles administered, and 84 and 168 days after the day of FU 1-PDFU 1 for participants in CR, PR, and SD.
Time Frame	Baseline, C1-D15, C2-D29, C2-D43, C3-D57, C4-D85, C5-D113, C6-D141, C7-D169, C8-D197, C9-D225, FU 1-PDFU 1 (28 days post Day 1 of Last Cycle), FU 85-PDFU 85 (84 days after FU-1), and FU 169-PDFU 169 (168 days after FU-1)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
CD5+CD19+, Cycle 1-Day 15, n=8	-71066.50 (114877.018)
CD5+CD19+, Cycle 2-Day 29, n=8	-50441.25 (56969.080)
CD5+CD19+, Cycle 2-Day 43, n=8	-36755.88 (36719.313)
CD5+CD19+, Cycle 3-Day 57, n=8	-31823.50 (37479.968)
CD5+CD19+, Cycle 4-Day 85, n=7	-35679.00 (39379.825)
CD5+CD19+, Cycle 5-Day 113, n=7	-35754.71 (39502.575)
CD5+CD19+, Cycle 6-Day 141, n=7	-35791.43 (39535.868)
CD5+CD19+, Cycle 7-Day 169, n=2	-61591.00 (19469.478)
CD5+CD19+, Cycle 8-Day 197, n=2	-61589.00 (19473.721)
CD5+CD19+, Cycle 9-Day 225, n=2	-61591.00 (19470.892)
CD5+CD19+, FU 1-PDFU 1, n=10	-59868.20 (96360.514)
CD5+CD19+, FU 85-PDFU 85, n=9	-31370.78 (36239.779)
CD5+CD19+, FU 169- PDFU 169, n=8	-31270.25 (38733.484)
CD19+CD5-, Cycle 1-Day 15, n=8	-6752.50 (14473.357)
CD19+CD5-, Cycle 2-Day 29, n=8	-6616.13 (14070.593)
CD19+CD5-, Cycle 2-Day 43, n=8	-6044.00 (12496.749)
CD19+CD5-, Cycle 3-Day 57, n=8	-2867.13 (4561.234)
CD19+CD5-, Cycle 4-Day 85, n=7	-1792.57 (3669.425)
CD19+CD5-, Cycle 5-Day 113, n=7	-1792.43 (3668.705)
CD19+CD5-, Cycle 6-Day 141, n=7	-1794.14 (3668.713)
CD19+CD5-, Cycle 7-Day 169, n=2	-362.50 (64.347)
CD19+CD5-, Cycle 8-Day 197, n=2	-362.00 (63.640)
CD19+CD5-, Cycle 9-Day 225, n=2	-362.00 (63.640)
CD19+CD5-, FU 1-PDFU 1, n=10	-7534.40 (13238.650)
CD19+CD5-, FU 85-PDFU 85, n=9	-3911.67 (6060.974)
CD19+CD5-, FU 169-PDFU 169, n=8	-2170.38 (3568.904)

18. Secondary Outcome

Title	Beta-2 Microglobulin at Cycle 1-Day 1
Description	Beta-2-microglobulin is a protein present on the surface of most cells. Higher levels indicate a poor prognosis of CLL. Beta-2 microglobulin was measured at Cycle 1-Day 1.
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Mean (Standard Deviation) [Nanomoles per liter (NMOL/L)]	301.442 (157.5521)

19. Secondary Outcome

Title	Complement (CH50) at Cycle 1-Day 1 and Cycle 4-Day 85
Description	The CH50 is the serum complement to lyse 50% of sensitized red blood cells; it is a marker of complement activation. A high CH50 level suggests evidence for complement activation, whereas a low CH50 level suggests lack of complement activation. Peripheral blood samples were collected for analysis at Cycle 1-Day 1 and Cycle 4-Day 85.
Time Frame	Cycle 1-Day 1 and Cycle 4-Day 85

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	10
Cycle 1-Day 1, n=10	42.63 (4.549)
Cycle 4-Day 85, n=7	39.80 (5.791)

20. Secondary Outcome

Title	Maximum (Peak) Plasma Concentration (Cmax) of Ofatumumab
Description	Maximum (peak) plasma drug concentration of ofatumumab was determined at Cycle 1-Day 1 and Cycle 3-Day 57. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr), and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).
Time Frame	Cycle 1-Day 1 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Overall Study Arm
Arm/Group Description	ar. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	59.4051
Cycle 3-Day 57, n=5	296.1851

21. Secondary Outcome

Title	Cmax of Serum Chlorambucil
Description	Cmax of serum chlorambucil was assesed at Cycle 1-Day 1, Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab +Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	412.1241
Cycle 1-Day 4, n=6	388.1516
Cycle 3-Day 57, n=5	420.9367

22. Secondary Outcome

Title	Cmax of Serum Phenyl Acetic Acid Mustard
Description	Cmax of chlorambucil metabolite phenyl acetic acid mustard was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	237.3587
Cycle 1-Day 4, n=6	215.5603
Cycle 3-Day 57, n=5	226.2480

23. Secondary Outcome

Title	Minimum Plasma Concentration (Cmin) of Ofatumumab
Description	Minimum plasma drug concentration of ofatumumab was determined at Cycle 1-Day 8, Cycle 2-Day 29, Cycle 3-Day 57, Cycle 4-Day 85, Cycle 5-Day 113, and Cycle 6-Day 141. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr), Cycle 2-Day 29 (pre-dose), Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr), Cycle 4-Day 85 (pre-dose, 30 min post end of infusion), Cycle 5-Day 113 (pre-dose and end of infusion) and Cycle 6-Day 141 (pre-dose and end of infusion).
Time Frame	Cycle 1-Day 8, Cycle 2-Day 29, Cycle 3-Day 57, Cycle 4-Day 85, Cycle 5-Day 113, and Cycle 6-Day 141

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 8, n=6	1.8693
Cycle 2-Day 29, n=4	73.0911
Cycle 3-Day 57, n=5	57.8542
Cycle 4-Day 85, n=4	82.1944
Cycle 5-Day 113, n=4	98.3353
Cycle 6-Day 141, n=4	82.9519

24. Secondary Outcome

Title	Cmin of Chlorambucil
Description	Cmin of chlorambucil was assesed at Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 4 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 4, n=6	NA
Cycle 3-Day 57, n=5	NA

25. Secondary Outcome

Title	Cmin of Phenyl Acetic Acid Mustard
Description	Cmin of chlorambucil metabolite phenyl acetic acid mustard was assesed at Cycle 1-Day 4 and Cycle 3-Day 57. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 4 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 4, n=6	NA
Cycle 3-Day 57, n=5	NA

26. Secondary Outcome

Title	Total Plasma Clearance (CL) of Ofatumumab
Description	Plasma clearance is defined as the plasma volume which is totally cleared of drug per unit of time. Blood samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Geometric Mean (95% Confidence Interval) [Milliliters/hour (mL/hr)]	172.64451

27. Secondary Outcome

Title	Area Under the Drug Plasma Concentration-time Curve From Dosing to Time Tau (AUC[0-tau]) of Ofatumumab
Description	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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. For ofatumumab it was assesed at Cycle 1-Day 1 and Cycle 3-Day 57. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).
Time Frame	Cycle 1-Day 1 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1438.65082
Cycle 3-Day 57, n=5	62463.2072

28. Secondary Outcome

Title	AUC(0-tau) of Chlorambucil
Description	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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1191.17448
Cycle 1-Day 4, n=6	1060.28140
Cycle 3-Day 57, n=5	1259.26147

29. Secondary Outcome

Title	AUC(0-tau) of Phenyl Acetic Acid Mustard
Description	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 drug plasma/serum concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of the drug. It was assesed at 1st (Cycle 1-Day 1), 4th (Cycle 1-Day 4), and 15th (Cycle 3-Day 57) chlorambucil administration. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Overall Study Arm
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1076.06435
Cycle 1-Day 4, n=6	984.02359
Cycle 3-Day 57, n=5	1038.87699

30. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-infinity]) for Ofatumumab
Description	The total AUC or AUC0-infinity is the area under the curve from time 0 extrapolated to infinite time. It was assesed on Cycle 1-Day 1. The samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Geometric Mean (95% Confidence Interval) [Hr*ug/mL]	1737.67475

31. Secondary Outcome

Title	AUC(0-infinity) for Chlorambucil
Description	The total AUC or AUC0-infinity is the area under the curve from time 0 extrapolated to infinite time. It was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1216.65216
Cycle 1-Day 4, n=6	1103.25854
Cycle 3-Day 57, n=5	1290.04709

32. Secondary Outcome

Title	AUC(0-infinity) for Phenyl Acetic Acid Mustard
Description	The total AUC or AUC(0-infinity) is the area under the curve from time 0 extrapolated to infinite time. It was assesed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1212.98123
Cycle 1-Day 4, n=6	1139.55544
Cycle 3-Day 57, n=5	1181.43279

33. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of Ofatumumab
Description	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. Samples were collected at Cycle 1-Day1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Geometric Mean (95% Confidence Interval) [mL]	5731.24330

34. Secondary Outcome

Title	Plasma Half-life (t1/2) of Ofatumumab
Description	t1/2 is the time required for the plasma concentration of ofatumumab to decrease by half. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).
Time Frame	Cycle 1-Day 1 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	33.69818
Cycle 3-Day 57, n=5	259.94722

35. Secondary Outcome

Title	Plasma Half-life (t1/2) of Chlorambucil
Description	t1/2 is the time required for the serum concentration of chlorambucil to decrease by half. Blood samples for serum concentration of chlorambucil was collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1.06879
Cycle 1-Day 4, n=6	1.74766
Cycle 3-Day 57, n=5	1.38140

36. Secondary Outcome

Title	Plasma Half-life (t1/2) of Phenyl Acetic Acid Mustard
Description	t1/2 is the time required for the plasma/serum concentration of phenylacetic acid mustard to decrease by half. Blood samples for serum concentration of phenylacetic acid mustard was collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	2.11378
Cycle 1-Day 4, n=6	2.52918
Cycle 3-Day 57, n=5	2.11552

37. Secondary Outcome

Title	Time to Maximum Concentration (Tmax) of Ofatumumab
Description	Tmax is the time required for reaching maximum concentration of drug (Cmax). Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr) and Cycle 3-Day 57 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr, 168 hr).
Time Frame	Cycle 1-Day 1 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	7.5400
Cycle 3-Day 57, n=5	5.3200

38. Secondary Outcome

Title	Time to Maximum Concentration (Tmax) of Chlorambucil
Description	Tmax is the time required for reaching maximum concentration of drug (Cmax). Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	2.9850
Cycle 1-Day 4, n=6	1.9850
Cycle 3-Day 57, n=5	3.0000

39. Secondary Outcome

Title	Time to Maximum Concentration (Tmax) of Phenyl Acetic Acid Mustard
Description	Tmax is the time required for reaching maximum concentration of drug (Cmax). Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	3.9600
Cycle 1-Day 4, n=6	3.4150
Cycle 3-Day 57, n=5	3.9200

40. Secondary Outcome

Title	Mean Residence Time to Infinity (MRTinf) of Ofatumumab
Description	MRTinf is the average amount of time that ofatumumab spends in the body. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Geometric Mean (95% Confidence Interval) [hours]	33.19679

41. Secondary Outcome

Title	Mean Residence Time Inf (MRTinf) of Chlorambucil
Description	MRTinf is the average amount of time that chlorambucil spends in the body. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	3.63147
Cycle 1-Day 4, n=6	3.36698
Cycle 3-Day 57, n=5	3.46924

42. Secondary Outcome

Title	Mean Residence Time Inf (MRTinf) of Phenyl Acetic Acid Mustard
Description	MRTinf is the average amount of time that phenyl acetic acid mustard spends in the body. Blood samples were collected at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	5.71852
Cycle 1-Day 4, n=6	5.62096
Cycle 3-Day 57, n=5	5.58632

43. Secondary Outcome

Title	Volume of Distribution (Vz) of Ofatumumab
Description	Vz for ofatumumab was calculated as a ratio of the amount of ofatumumab in the body during the terminal phase to the plasma concentration during the terminal phase. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1hr, 2 hr, 24 hr, 72 hr, 120 hr).
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Geometric Mean (95% Confidence Interval) [mL]	8393.31979

44. Secondary Outcome

Title	Apparent Total Clearance of the Drug From Plasma (CL/F) for Chlorambucil
Description	CL/F is defined as the apparent total clearance of the drug from plasma after oral administration of chlorambucil. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	8.21928
Cycle 1-Day 4, n=6	9.06406
Cycle 3-Day 57, n=5	7.75166

45. Secondary Outcome

Title	Apparent Volume of Distribution During Terminal Phase (Vz/F) of Chlorambucil
Description	Vz/F of chlorambucil is defined as the apparent volume of distribution during terminal phase after non-intravenous (oral) administration of chlorambucil. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	12.67367
Cycle 1-Day 4, n=6	22.85356
Cycle 3-Day 57, n=5	15.44858

46. Secondary Outcome

Title	%AUC_extrap of Ofatumumab
Description	%AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. Samples were collected at Cycle 1-Day 1 (pre-dose, end of infusion, 10 min, 1 hr, 2 hr, 24 hr, 72 hr, 120 hr).
Time Frame	Cycle 1-Day 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Geometric Mean (95% Confidence Interval) [percentage of AUC after extrapolation]	3.99041

47. Secondary Outcome

Title	%AUC_extrap of Chlorambucil
Description	%AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	1.51853
Cycle 1-Day 4, n=6	3.20042
Cycle 3-Day 57, n=5	2.01046

48. Secondary Outcome

Title	%AUC_extrap of Phenyl Acetic Acid Mustard
Description	%AUC_extrap is defined as the area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	10.12009
Cycle 1-Day 4, n=6	11.57955
Cycle 3-Day 57, n=5	8.34549

49. Secondary Outcome

Title	AUC (0-t) of Ofatumumab
Description	AUC (0-t) represents the area under the concentration curve of ofatumumab in plasma from 0 to time t hours. AUC (0-t) was assessed at 168 hours and 672 hours post-dose.
Time Frame	Cycle 1-Day 1 and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
AUC(0-168), Cycle 1-Day 1, n=6	1526.32835
AUC (0-672), Cycle 3-Day 57, n=5	58769.6326

50. Secondary Outcome

Title	AUC (0-t) of Chlorambucil
Description	AUC (0-t) represents the area under the concentration curve of chlorambucil in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
AUC(0-6), Cycle 1-Day 1, n=6	1069.26703
AUC(0-6), Cycle 1-Day 4, n=6	956.95261
AUC(0-6), Cycle 3-Day 57, n=5	1139.48401
AUC(0-24), Cycle 1-Day 1, n=6	1216.41085
AUC(0-24), Cycle 1-Day 4, n=6	1102.61367
AUC(0-24), Cycle 3-Day 57, n=5	1289.89389

51. Secondary Outcome

Title	AUC (0-t) of Phenyl Acetic Acid Mustard
Description	AUC (0-t) represents the area under the concentration curve of phenyl acetic acid mustard in serum from 0 to time t hours. AUC (0-t) was assessed at 6 hours and 24 hours.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
AUC(0-6), Cycle 1-Day 1, n=6	755.55297
AUC(0-6), Cycle 1-Day 4, n=6	719.39401
AUC(0-6), Cycle 3-Day 57, n=5	743.47268
AUC(0-24), Cycle 1-Day 1, n=6	1211.58911
AUC(0-24), Cycle 1-Day 4, n=6	1134.84945
AUC(0-24), Cycle 3-Day 57, n=5	1175.00443

52. Secondary Outcome

Title	Dose Normalized Cmax (Cmax/D) for Chlorambucil
Description	Cmax/D is defined as the maximum plasma concentration (Cmax) per unit dose. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4 and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	26.49755
Cycle 1-Day 4, n=6	24.95624
Cycle 3-Day 57, n=5	28.82981

53. Secondary Outcome

Title	Cmax/D for Phenyl Acetic Acid Mustard
Description	Cmax/D is defined as the maximum plasma concentration (Cmax) per unit dose. It was assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
Cycle 1-Day 1, n=6	15.26100
Cycle 1-Day 4, n=6	13.85946
Cycle 3-Day 57, n=5	15.49565

54. Secondary Outcome

Title	AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D, and AUC (0-tau)/D of Chlorambucil
Description	Dose adjusted AUC for the indicated time points were assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
AUC(0-6)/D, Cycle 1-Day 1, n=6	68.74861
AUC(0-6)/D, Cycle 1-Day 4, n=6	61.52734
AUC(0-6)/D, Cycle 3-Day 57, n=5	78.04287
AUC(0-24)/D, Cycle 1-Day 1, n=6	78.20923
AUC(0-24)/D, Cycle 1-Day 4, n=6	70.89263
AUC(0-24)/D, Cycle 3-Day 57, n=5	88.34439
AUC(0-tau)/D, Cycle 1-Day 1, n=6	76.58665
AUC(0-tau)/D, Cycle 1-Day 4, n=6	68.17087
AUC(0-tau)/D, Cycle 3-Day 57, n=5	86.24639
AUC(0-inf)/D, Cycle 1-Day 1, n=6	78.22474
AUC(0-inf)/D, Cycle 1-Day 4, n=6	70.93409
AUC(0-inf)/D, Cycle 3-Day 57, n=5	88.35489

55. Secondary Outcome

Title	AUC (0-6)/D, AUC(0-24)/D, AUC (0-inf)/D and AUC (0-tau)/D of Phenyl Acetic Acid Mustard
Description	Dose adjusted AUC for the indicated time points were assessed at Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57. In each sampling, blood samples were collected at pre-dose, and 15 min, 30 min, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, and 10 hr.
Time Frame	Cycle 1-Day 1, Cycle 1-Day 4, and Cycle 3-Day 57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ofatumumab + Chlorambucil
Arm/Group Description	Par. with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28-day cycle in combination with oral chlorambucil 10 mg/meter squared (m^2) on Days 1-7 of each cycle for at least 3 cycles, until best overall response or up to 12 cycles. After the Treatment Phase (for par. in CR, PR or SD), survival and disease status were assessed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 and 168 days after the day of FU1 (FU85 and FU169, respectively). For par. with disease progression (PD) during the Treatment Phase, post PD follow-up were done 28 days after the first day of the last treatment cycle (PDFU1) to assess safety. Survival status, date of next CLL therapy, and type of therapy were subsequently assessed 84 and 168 days after the day of PDFU1 (PDFU85 and PDFU169, respectively).
Measure Participants	6
AUC(0-6)/D, Cycle 1-Day 1, n=6	48.57834
AUC(0-6)/D, Cycle 1-Day 4, n=6	46.25349
AUC(0-6)/D, Cycle 3-Day 57, n=5	50.92019
AUC(0-24)/D, Cycle 1-Day 1, n=6	77.89921
AUC(0-24)/D, Cycle 1-Day 4, n=6	72.96523
AUC(0-24)/D, Cycle 3-Day 57, n=5	80.47565
AUC(0-tau)/D, Cycle 1-Day 1, n=6	69.18564
AUC(0-tau)/D, Cycle 1-Day 4, n=6	63.26787
AUC(0-tau)/D, Cycle 3-Day 57, n=5	71.15233
AUC(0-inf)/D, Cycle 1-Day 1, n=6	77.98872
AUC(0-inf)/D, Cycle 1-Day 4, n=6	73.26780
AUC(0-inf)/D, Cycle 3-Day 57, n=5	80.91593

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment until follow-up for survival (up to Week 62.3).
Adverse Event Reporting Description	SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who received at least one dose of investigational product.
Arm/Group Title	Ofatumumab+Chlorambucil
Arm/Group Description	Participants with previously untreated chronic lymphocytic leukemia (CLL) received intravenous (IV) infusions of ofatumumab on Day 1 (300 milligrams [mg]) and Day 8 (1000 mg) in the first cycle, followed by 1000 mg on the first day of each subsequent 28 day cycle in combination with chlorambucil 10 mg/meter squared (m^2) orally on Days 1-7 of every 28 day cycle for a minimum of 3 cycles, until best overall response or a maximum of 12 cycles. After completion of the Treatment Phase (for participants in CR, PR or SD), survival and disease status assessment visits were performed 28 days after the first day of the last treatment cycle (Follow-up [FU] 1), 84 days, and 168 days after the day of FU 1 (FU 85 and FU 169, respectively). For participants experiencing disease progression during the Treatment Phase, the post progressive disease (PD) follow-up for safety assessments were performed 28 days after the first day of the last treatment cycle (PDFU 1). Subsequent follow-up was performed 8
All Cause Mortality
	Ofatumumab+Chlorambucil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ofatumumab+Chlorambucil
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Injury, poisoning and procedural complications
Spinal compression fracture	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/10 (10%)
Other (Not Including Serious) Adverse Events
	Ofatumumab+Chlorambucil
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	7/10 (70%)
Neutropenia	5/10 (50%)
Anaemia	3/10 (30%)
Cardiac disorders
Palpitations	1/10 (10%)
Gastrointestinal disorders
Nausea	5/10 (50%)
Constipation	2/10 (20%)
Abdominal pain upper	1/10 (10%)
Diarrhoea	1/10 (10%)
Enterocolitis	1/10 (10%)
Vomiting	1/10 (10%)
General disorders
Fatigue	3/10 (30%)
Pyrexia	3/10 (30%)
Chills	2/10 (20%)
Oedema	2/10 (20%)
Chest discomfort	1/10 (10%)
Malaise	1/10 (10%)
Hepatobiliary disorders
Hepatic function abnormal	1/10 (10%)
Infections and infestations
Nasopharyngitis	2/10 (20%)
Herpes zoster	1/10 (10%)
Otitis media	1/10 (10%)
Investigations
White blood cell count decreased	5/10 (50%)
Neutrophil count decreased	4/10 (40%)
Platelet count decreased	3/10 (30%)
Alanine aminotransferase increased	2/10 (20%)
Aspartate aminotransferase increased	2/10 (20%)
Weight decreased	2/10 (20%)
Weight increased	2/10 (20%)
Amylase increased	1/10 (10%)
Beta 2 microglobulin increased	1/10 (10%)
Blood bilirubin increased	1/10 (10%)
Blood creatinine increased	1/10 (10%)
Blood lactate dehydrogenase increased	1/10 (10%)
Blood phosphorus increased	1/10 (10%)
Blood potassium increased	1/10 (10%)
Blood sodium decreased	1/10 (10%)
Electrocardiogram ST segment depression	1/10 (10%)
Haemoglobin decreased	1/10 (10%)
Lymphocyte count decreased	1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	4/10 (40%)
Musculoskeletal and connective tissue disorders
Back pain	1/10 (10%)
Bone pain	1/10 (10%)
Neck pain	1/10 (10%)
Spinal column stenosis	1/10 (10%)
Nervous system disorders
Headache	2/10 (20%)
Dizziness	1/10 (10%)
Dysgeusia	1/10 (10%)
Psychiatric disorders
Insomnia	2/10 (20%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/10 (20%)
Hypoxia	2/10 (20%)
Wheezing	1/10 (10%)
Skin and subcutaneous tissue disorders
Rash	6/10 (60%)
Pruritus	3/10 (30%)
Dermatitis acneiform	2/10 (20%)
Rash maculo-papular	2/10 (20%)
Vascular disorders
Hot flush	1/10 (10%)
Hypertension	1/10 (10%)
Hypotension	1/10 (10%)

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.