Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01313689
• Collaborator: (none)
• Enrollment: 122
• Locations: 80
• Arms: 2
• Actual Duration (Months): 72.3
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study was to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study compared ofatumumab with the physicians' choice of therapy.

Condition or Disease	Intervention/Treatment	Phase
Leukaemia	Drug: Ofatumumab; Drug: Physicians' Choice	Phase 3

Detailed Description

Patients with CLL that is refractory to fludarabine have few treatment options and a poor prognosis. There is a continued need for new therapies for these CLL patients, as demonstrated by the limited responses and substantial toxicities with existing therapies. This is supported by the lack of a consensus around standard of care treatment for CLL patients with bulky fludarabine-refractory disease. The objective of this study was to confirm the response rate and disease control in the refractory setting through a controlled trial comparing ofatumumab with the physicians' choice of therapy in fludarabine-refractory, bulky lymphadenopathy patients. After 24 weeks of treatment with ofatumumab, patients were further randomized to either extended ofatumumab treatment or observation. Patients on the physicians' choice arm had the option of receiving ofatumumab if they experience progressive disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy Versus Physicians' Choice in Patients With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukaemia (CLL)
• Actual Study Start Date: Apr 14, 2011
• Actual Primary Completion Date: Mar 18, 2014
• Actual Study Completion Date: Apr 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ofatumumab Biological	Drug: Ofatumumab; Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).
Active Comparator: Physicians' Choice Physicians' choice of treatment	Drug: Physicians' Choice; Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC) [From the randomization date up to 60 months post the randomization date.]

   PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.

Secondary Outcome Measures

1. Progression-free Survival (PFS) as Assessed by Investigator [From the randomization date up to 60 months post the randomization date.]

   PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.

2. Overall Response Rate (ORR) as Assessed by the IRC [From the randomization date up to 60 months post the randomization date.]

   ORR is defined as the number of participants achieving either complete response (CR) or partial response (PR). ORR was measured using the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria: no lymphadenopathy(Ly)/ hepatomegaly, splenomegaly, constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC and no lymphoid nodules. PR requires the following criteria for at least 2 months: >=50% decrease in LC, reduction in Ly (i.e., >=50% decrease in lymph node size or no increase or new lymph nodes), >=50% decrease in the size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL, neutrophils>1500/μL. Nodular PR (nPR) indicates persistent nodules in the BM.

3. Overall Response Rate (ORR) as Assessed by the Investigator [From the randomization date up to 60 months post the randomization date.]

   ORR is defined as the number of participants achieving either complete response (CR) or partial response (PR). Overall response was measured using the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria: no lymphadenopathy(Ly)/ hepatomegaly, splenomegaly, constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC and no lymphoid nodules. PR requires the following criteria for at least 2 months: >=50% decrease in LC, reduction in Ly (i.e., >=50% decrease in lymph node size or no increase or new lymph nodes), >=50% decrease in the size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL, neutrophils>1500/μL. Nodular PR (nPR) indicates persistent nodules in the BM.

4. Overall Survival [From the randomization date up to 60 months post the randomization date.]

   Overall survival (OS) is defined as the time from randomization to death due to any cause. Kaplan-Meier plots were used to estimate the reported median OS time.

5. Time to Progression as Assessed by IRC [From the randomization date up to 60 months post the randomization date.]

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

6. Time to Next Anti-cancer Therapy by Investigator [From the randomization date up to 60 months post the randomization date.]

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

7. Time to Response as Assessed by the IRC [From the randomization date up to 60 months post the randomization date.]

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

8. Duration of Response as Assessed by the IRC [From the randomization date up to 60 months post the randomization date.]

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

9. Number of Participants With Any Adverse Event (AE), Any Serious Adverse Event (SAE), Any Fatal Serious Adverse Event (FSAE), or Deaths [From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy]

   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. A 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 or incapacity, is a congenital anomaly or birth defect.

10. Number of Participants With Any Adverse Event (AE) of Special Interest [From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy]

    AEs of special interest included cytopenias (neutropenia [decreased neutrophil count], anaemia [decreased hemoglobin], and thrombocytopenia [decreased platelet count]), autoimmune haematologic complications (autoimmune haemolytic anaemia and haemolytic anaemia), infusion reactions, infections, mucocutaneous reactions, Tumour Lysis Syndrome (TLS), cardiovascular events, and small bowel obstruction.

11. Mean Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Over Time [Screening and every 3 months during treatment, every 6 months after last treatment until PD or until 42 Month Follow-up Visit]

    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. Immunoglobulin testing was performed at Screening (SCR), Cycle 3 Week 4 (C3W4), Cycle 7 Week 4 (C3W4) ,Cycle 9 Week 4 (C3W4), 6 Month Follow-up Visit (6M FU), 9 Month Follow-up (9M FU), 12 Month Follow-up (12M FU), 18 Month Follow-up (18M FU), 24 Month Follow-up (24M FU), 30 Month Follow-up (30M FU), 36 Month Follow-up (36M FU), 42 Month Follow-up (42M FU). A cycle is defined as the time between one round of treatment until the start of the next round.

12. Number of Participants Who Were Positive or Negative for Human Anti-Human Antibodies (HAHA) Post-OFA Therapy [From the randomization date up to 60 months post the randomization date.]

    The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. All samples were first assessed in a screening (SCR) assay, and the potential positive (Pos) samples were further tested in the confirmation (CNF) assays. Confirmed positives were reported as HAHA positive and titer was determined for each positive sample. The drug tolerance of the HAHA assay is 200 microgram/milliliter (µg/mL); thus, samples that tested negative in the assay and had ofatumumab concentrations no more than 200 µg/mL were considered as conclusive negative (Neg) results.

13. Changes From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16) [From the randomization date up to 60 months post the randomization date.]

    The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales - fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection (4 items) - and single item scales (social activities [Social Problems (SP) Scale] and future health worries[Future Health (FH) Scale].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 - 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Week (W) 12 (W4 of Cycle[C] 3), W24 (W4C6), W36 (W4C9), W48 (W4C13); during Follow-up which was every month for Months (M) 1-6, every 8 weeks for M7-12 and every 3 months up to M60; and then at PD.

14. Mean Health Change Questionnaire (HCQ) Score [From the randomization date up to 60 months post the randomization date.]

    The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. A score of 3 or less indicates improvement from Baseline. HCQ was assessed at Screening; Week (W) 12 (W4 of Cycle[C] 3), W24 (W4C6), W36 (W4C9), W48 (W4C13); during follow-up which was every month for Months 1-6, every 8 weeks for M7-12 and every 3 months up to M60; and then at PD..

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults with documented diagnosis of active CLL requiring treatment

• Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm

• Must be refractory to fludarabine treatment

• Age 18 yrs or older

• At least 2 prior therapies for CLL

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Signed written informed consent

Exclusion Criteria:

• Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months

• Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study

• CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL

• Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment

• Human immunodeficiency virus (HIV) positive

• Significant concurrent, uncontrolled medical condition

• Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry

• Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone

• Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL)

• Known or suspected hypersensitivity to ofatumumab

• Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Graz		Austria	8036
2	Novartis Investigative Site	Innsbruck		Austria	6020
3	Novartis Investigative Site	Linz		Austria	4020
4	Novartis Investigative Site	Salzburg		Austria	A-5020
5	Novartis Investigative Site	Wien		Austria	1140
6	Novartis Investigative Site	Bruxelles		Belgium	1200
7	Novartis Investigative Site	Leuven		Belgium	3000
8	Novartis Investigative Site	Sofia		Bulgaria	1233
9	Novartis Investigative Site	Sofia		Bulgaria	1407
10	Novartis Investigative Site	Sofia		Bulgaria	1431
11	Novartis Investigative Site	Hradec Kralove		Czechia
12	Novartis Investigative Site	Olomouc		Czechia	775 20
13	Novartis Investigative Site	Praha 2		Czechia	128 08
14	Novartis Investigative Site	Bobigny cedex		France	93009
15	Novartis Investigative Site	Brest cedex		France	29609
16	Novartis Investigative Site	Clermont-Ferrand Cedex 1		France	63003
17	Novartis Investigative Site	Creteil cedex		France	94010
18	Novartis Investigative Site	Lille cedex		France	59037
19	Novartis Investigative Site	Rennes cedex 9		France	35033
20	Novartis Investigative Site	Toulouse cedex 9		France	31059
21	Novartis Investigative Site	Tours cedex 9		France	37044
22	Novartis Investigative Site	Kronach	Bayern	Germany	96317
23	Novartis Investigative Site	Regensburg	Bayern	Germany	93053
24	Novartis Investigative Site	Frankfurt/Oder	Brandenburg	Germany	15236
25	Novartis Investigative Site	Frankfurt	Hessen	Germany	60590
26	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45122
27	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
28	Novartis Investigative Site	Koblenz	Rheinland-Pfalz	Germany	56068
29	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt	Germany	39130
30	Novartis Investigative Site	Chemnitz	Sachsen	Germany	09113
31	Novartis Investigative Site	Dresden	Sachsen	Germany	01307
32	Novartis Investigative Site	Budapest		Hungary	1097
33	Novartis Investigative Site	Debrecen		Hungary	4012
34	Novartis Investigative Site	Pecs		Hungary	7624
35	Novartis Investigative Site	Szombathely		Hungary	9700
36	Novartis Investigative Site	Dublin		Ireland	7
37	Novartis Investigative Site	Galway		Ireland
38	Novartis Investigative Site	James Street		Ireland	8
39	Novartis Investigative Site	Jerusalem		Israel	91120
40	Novartis Investigative Site	Ramat Gan		Israel	52621
41	Novartis Investigative Site	Modena	Emilia-Romagna	Italy	41124
42	Novartis Investigative Site	Brescia	Lombardia	Italy	25123
43	Novartis Investigative Site	Milano	Lombardia	Italy	20132
44	Novartis Investigative Site	Milano	Lombardia	Italy	20162
45	Novartis Investigative Site	Torino	Piemonte	Italy	10126
46	Novartis Investigative Site	Messina	Sicilia	Italy	95158
47	Novartis Investigative Site	Chorzow		Poland	41-500
48	Novartis Investigative Site	Lodz		Poland	93-510
49	Novartis Investigative Site	Wroclaw		Poland	50-367
50	Novartis Investigative Site	Chelyabinsk		Russian Federation	454076
51	Novartis Investigative Site	Moscow		Russian Federation	115478
52	Novartis Investigative Site	St'Petersburg		Russian Federation	197341
53	Novartis Investigative Site	St. Petersburg		Russian Federation	198205
54	Novartis Investigative Site	Singapore		Singapore	169608
55	Novartis Investigative Site	Bratislava		Slovakia	833 10
56	Novartis Investigative Site	Bratislava		Slovakia	851 07
57	Novartis Investigative Site	Kosice		Slovakia	041 66
58	Novartis Investigative Site	Martin		Slovakia	036 59
59	Novartis Investigative Site	Goteborg		Sweden	SE-413 45
60	Novartis Investigative Site	Linkoping		Sweden	SE-581 85
61	Novartis Investigative Site	Lulea		Sweden	SE-971 80
62	Novartis Investigative Site	Orebro		Sweden	SE-701 85
63	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
64	Novartis Investigative Site	Umea		Sweden	SE-901 85
65	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
66	Novartis Investigative Site	Cherkasy		Ukraine	18009
67	Novartis Investigative Site	Dnipropetrovsk		Ukraine	49102
68	Novartis Investigative Site	Donetsk		Ukraine	83045
69	Novartis Investigative Site	Kharkiv		Ukraine	61070
70	Novartis Investigative Site	Khmelnytskyi		Ukraine	29000
71	Novartis Investigative Site	Kyiv		Ukraine	03022
72	Novartis Investigative Site	Kyiv		Ukraine	04112
73	Novartis Investigative Site	Lviv		Ukraine	79044
74	Novartis Investigative Site	Makiivka		Ukraine	86132
75	Novartis Investigative Site	Simferopil		Ukraine	95023
76	Novartis Investigative Site	Vinnitsa		Ukraine	21018
77	Novartis Investigative Site	Zhytomyr		Ukraine	10002
78	Novartis Investigative Site	Bournemouth		United Kingdom	BH7 7DW
79	Novartis Investigative Site	Manchester		United Kingdom	M20 4BX
80	Novartis Investigative Site	Oxford		United Kingdom	OX3 7LE

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01313689
• Other Study ID Numbers: 114242
• First Posted: Mar 14, 2011
• Last Update Posted: Nov 8, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: OMB157; Lymphocytic; Chronic; Safety; Refractory; Chronic Lymphocytic Leukemia; Oncology; Ofatumumab; Efficacy; Physicians' Choice; Bulky Fludarabine Refractory Chronic Lymphocytic Leukemia; CLL
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Ofatumumab

Study Results

Participant Flow

Recruitment Details	Note: The 'Total Participants' in the Baseline Characteristics Table and in most of the Efficacy results Tables should be either Any OFA + Physician's Choice or OFA extended + OFA observation + OFA + Physician's Choice instead of the automatic calculated Total number indicated.
Pre-assignment Detail	Participants(par) were randomized to receive an Open-Label treatment(trt) of ofatumumab(OFA) or a physicians choice(PC) trt for up to 24 weeks. OFA par without progressive disease(PD) underwent a second randomization to receive an additional 24 weeks of OFA or no further trt. PC par who developed PD had the option to receive OFA salvage therapy.

Arm/Group Title	Any Ofatumumab	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Period Title: 24-Week Randomization 1
STARTED	79	43	0	0	0
COMPLETED	60	33	0	0	0
NOT COMPLETED	19	10	0	0	0
Period Title: 24-Week Randomization 1
STARTED	0	0	24	13	42
COMPLETED	0	0	21	12	27
NOT COMPLETED	0	0	3	1	15

Baseline Characteristics

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)	Total
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Total of all reporting groups
Overall Participants	79	43	24	13	42	201
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.3 (8.95)	61.8 (9.87)	61.7 (9.09)	66.7 (5.99)	63.2 (9.52)	62.8 (9.28)
Sex: Female, Male (Count of Participants)
Female	24 30.4%	14 32.6%	9 37.5%	2 15.4%	13 31%	62 30.8%
Male	55 69.6%	29 67.4%	15 62.5%	11 84.6%	29 69%	139 69.2%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	1 1.3%	0 0%	0 0%	0 0%	1 2.4%	2 1%
Not Hispanic or Latino	78 98.7%	43 100%	24 100%	13 100%	41 97.6%	199 99%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC)
Description	PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all participants who were randomised to receive OFA or PC at the first randomisation.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	These participants came from the Physicia's Choice (PC) arm. Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13
Median (95% Confidence Interval) [Months]	5.36	3.61	10.05	7.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Any Ofatumumab (OFA), Physician's Choice (PC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2677
	Comments
	Method	Log Rank
	Comments	P-value is based on the stratified log-rank test adjusted for 'interval' and pooled stratum
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios are estimated using the Pike estimator, adjusted for 'interval' and pooled stratum

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab Extended (OFA Ext), Ofatumumab Observation (OFA Observ.)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0837
	Comments
	Method	Log Rank
	Comments	P-value is based on the stratified log-rank test adjusted for 'interval' and pooled stratum
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.19 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios are estimated using the Pike estimator, adjusted for 'interval' and pooled stratum

2. Secondary Outcome

Title	Progression-free Survival (PFS) as Assessed by Investigator
Description	PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all participants who were randomised to receive OFA or PC at the first randomisation.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13
Median (95% Confidence Interval) [Months]	7.00	4.50	12.68	9.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Any Ofatumumab (OFA), Physician's Choice (PC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0030
	Comments
	Method	Log Rank
	Comments	P-value is based on the stratified log-rank test adjusted for 'interval' and pooled stratum
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.35 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios are estimated using the Pike estimator, adjusted for 'interval' and pooled stratum.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab Extended (OFA Ext), Ofatumumab Observation (OFA Observ.)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0262
	Comments
	Method	Log Rank
	Comments	P-value is based on the stratified log-rank test adjusted for 'interval' and pooled stratum
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios are estimated using the Pike estimator, adjusted for 'interval' and pooled stratum

3. Secondary Outcome

Title	Overall Response Rate (ORR) as Assessed by the IRC
Description	ORR is defined as the number of participants achieving either complete response (CR) or partial response (PR). ORR was measured using the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria: no lymphadenopathy(Ly)/ hepatomegaly, splenomegaly, constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC and no lymphoid nodules. PR requires the following criteria for at least 2 months: >=50% decrease in LC, reduction in Ly (i.e., >=50% decrease in lymph node size or no increase or new lymph nodes), >=50% decrease in the size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL, neutrophils>1500/μL. Nodular PR (nPR) indicates persistent nodules in the BM.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

ITT Population. Not evaluable is defined as insufficient data present to classify into one of the other categories.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13
CR	0 0%	0 0%	0 0%	0 0%
PR	30 38%	7 16.3%	18 75%	8 61.5%
nPR	0 0%	0 0%	0 0%	0 0%
Stable Disease	36 45.6%	22 51.2%	5 20.8%	5 38.5%
Progressive Disease	9 11.4%	8 18.6%	1 4.2%	0 0%
Not Evaluable	4 5.1%	6 14%	0 0%	0 0%
Missing	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Any Ofatumumab (OFA), Physician's Choice (PC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0223
	Comments
	Method	Regression, Logistic
	Comments	conditional logistic regression with interval and pooled stratum
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.942
	Confidence Interval	(2-Sided) 95%; 1.166 to 7.424
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab Extended (OFA Ext), Ofatumumab Observation (OFA Observ.)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9985
	Comments
	Method	Regression, Logistic
	Comments	conditional logistic regression with interval and pooled stratum
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	999.999
	Confidence Interval	(2-Sided) 95%; 0.001 to 999.999
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Overall Response Rate (ORR) as Assessed by the Investigator
Description	ORR is defined as the number of participants achieving either complete response (CR) or partial response (PR). Overall response was measured using the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria: no lymphadenopathy(Ly)/ hepatomegaly, splenomegaly, constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC and no lymphoid nodules. PR requires the following criteria for at least 2 months: >=50% decrease in LC, reduction in Ly (i.e., >=50% decrease in lymph node size or no increase or new lymph nodes), >=50% decrease in the size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL, neutrophils>1500/μL. Nodular PR (nPR) indicates persistent nodules in the BM.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

ITT Population. Not evaluable is defined as insufficient data present to classify into one of the other categories.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13	42
CR	2 2.5%	2 4.7%	1 4.2%	1 7.7%	0 0%
PR	36 45.6%	12 27.9%	17 70.8%	7 53.8%	12 28.6%
nPR	1 1.3%	2 4.7%	0 0%	1 7.7%	0 0%
Stable Disease	34 43%	14 32.6%	6 25%	4 30.8%	24 57.1%
Progressive Disease	2 2.5%	10 23.3%	0 0%	0 0%	2 4.8%
Not Evaluable	0 0%	0 0%	0 0%	0 0%	0 0%
Missing	4 5.1%	3 7%	0 0%	0 0%	4 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Any Ofatumumab (OFA), Physician's Choice (PC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4159
	Comments	Odds ratios and p-value are based on conditional logistic regression with interval and pooled stratum included in the Strata statement
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.366
	Confidence Interval	(2-Sided) 95%; 0.644 to 2.899
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab Extended (OFA Ext), Ofatumumab Observation (OFA Observ.)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8866
	Comments	Odds ratios and p-value are based on conditional logistic regression with interval and pooled stratum in the strata statement
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.225
	Confidence Interval	(2-Sided) 95%; 0.076 to 19.862
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) is defined as the time from randomization to death due to any cause. Kaplan-Meier plots were used to estimate the reported median OS time.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available were analyzed, participants who had not died were censored at the date of last contact.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13	42
Median (95% Confidence Interval) [Months]	19.19	14.52	31.54	45.50	8.57

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Any Ofatumumab (OFA), Physician's Choice (PC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1732
	Comments
	Method	Log Rank
	Comments	P-value is based on the stratified log-rank test adjusted for 'interval' and pooled stratum
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios are estimated using the Pike estimator, adjusted for 'interval' and pooled stratum

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab Extended (OFA Ext), Ofatumumab Observation (OFA Observ.)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8128
	Comments	P-value is based on the stratified log-rank test adjusted for 'interval' and pooled stratum
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.46 to 2.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios are estimated using the Pike estimator, adjusted for 'interval' and pooled stratum

6. Secondary Outcome

Title	Time to Progression as Assessed by IRC
Description	Time to progression is defined as the time from the date of randomization to disease progression (PD). PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Participants who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time were censored at the date of the last visit with adequate assessment.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available were analyzed.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	56	23	19	11
Median (95% Confidence Interval) [Months]	6.31	5.32	10.05	7.16

7. Secondary Outcome

Title	Time to Next Anti-cancer Therapy by Investigator
Description	Time to next therapy is defined as the time from randomization until the start of the next line of treatment.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available were analyzed.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	44	29	12	12
Median (95% Confidence Interval) [Months]	11.50	6.54	15.47	9.00

8. Secondary Outcome

Title	Time to Response as Assessed by the IRC
Description	Time to response is defined as the time from randomization to the first response (Complete Remission[CR], Complete Remission with incomplete bone marrow recovery[CRi], partial response[PR], or nodular PR[nPR]). CR(all the criteria at least 2 months after last treatment): no lymphadenopathy(Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. Participants with unknown or missing responses were considered as non-responders.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

ITT population. Only responders (CR, CRi, PR, nPR) were included in the analysis. Response was measured using the International Workshop for CLL (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines 2008.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	30	7	18	8
Median (95% Confidence Interval) [Months]	1.17	2.56	1.86	1.15

9. Secondary Outcome

Title	Duration of Response as Assessed by the IRC
Description	DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time (>= 12 weeks) were censored at the date of the last visit with adequate assessment. Par. with unknown or missing responses were considered as non-responders.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.
Measure Participants	23	5
Median (95% Confidence Interval) [Months]	6.24	6.95

10. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE), Any Serious Adverse Event (SAE), Any Fatal Serious Adverse Event (FSAE), or Deaths
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. A 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 or incapacity, is a congenital anomaly or birth defect.
Time Frame	From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least one dose of any study treatment (OFA or PC) at the first randomization.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)	OFA Salvage
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	The participants in this arm are from the Physician's Choice (PC) arm. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	78	43	24	13	41	22
Any AE	71 89.9%	37 86%	22 91.7%	10 76.9%	39 92.9%	20 10%
Any SAE	43 54.4%	23 53.5%	12 50%	5 38.5%	26 61.9%	10 5%
Any FSAE	14 17.7%	6 14%	2 8.3%	3 23.1%	9 21.4%	5 2.5%
Deaths	1 1.3%	0 0%	0 0%	0 0%	1 2.4%	0 0%

11. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) of Special Interest
Description	AEs of special interest included cytopenias (neutropenia [decreased neutrophil count], anaemia [decreased hemoglobin], and thrombocytopenia [decreased platelet count]), autoimmune haematologic complications (autoimmune haemolytic anaemia and haemolytic anaemia), infusion reactions, infections, mucocutaneous reactions, Tumour Lysis Syndrome (TLS), cardiovascular events, and small bowel obstruction.
Time Frame	From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least one dose of any study treatment (OFA or PC) at the first randomization.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	78	43	24	13
Any AE of decreased neutrophil count	23 29.1%	15 34.9%	11 45.8%	2 15.4%
Any AE of decreased hemoglobin	9 11.4%	9 20.9%	3 12.5%	2 15.4%
Any AE of decreased platelet count	10 12.7%	5 11.6%	3 12.5%	1 7.7%
Any AE of autoimmune haemolytic anaemia	0 0%	2 4.7%	0 0%	0 0%
Any AE of haemolytic anaemia	1 1.3%	0 0%	1 4.2%	0 0%
Any infusion related AE	33 41.8%	11 25.6%	8 33.3%	4 30.8%
Any AE of Infection	46 58.2%	24 55.8%	16 66.7%	8 61.5%
Any AE of mucocutaneous reaction	20 25.3%	4 9.3%	6 25%	3 23.1%
Any AE of TLS	1 1.3%	1 2.3%	0 0%	0 0%
Any AE of cardiovascular events	13 16.5%	3 7%	6 25%	0 0%
Any AE of small bowel obstruction	0 0%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Mean Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Over Time
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. Immunoglobulin testing was performed at Screening (SCR), Cycle 3 Week 4 (C3W4), Cycle 7 Week 4 (C3W4) ,Cycle 9 Week 4 (C3W4), 6 Month Follow-up Visit (6M FU), 9 Month Follow-up (9M FU), 12 Month Follow-up (12M FU), 18 Month Follow-up (18M FU), 24 Month Follow-up (24M FU), 30 Month Follow-up (30M FU), 36 Month Follow-up (36M FU), 42 Month Follow-up (42M FU). A cycle is defined as the time between one round of treatment until the start of the next round.
Time Frame	Screening and every 3 months during treatment, every 6 months after last treatment until PD or until 42 Month Follow-up Visit

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least one dose of any study treatment (OFA or PC) at the first randomization.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)	OFA Salvage
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	The participants in this arm are from the Physician's Choice (PC) arm. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	78	43	24	13	41	22
IgA, SCR	0.793 (0.6680)	0.685 (0.5518)	0.807 (0.7426)	1.095 (0.7535)	0.688 (0.5749)
IgG, SCR	6.909 (4.6836)	8.615 (12.1625)	6.270 (3.8573)	8.128 (4.7569)	6.898 (5.1142)
IgM, SCR	0.800 (1.3154)	0.601 (0.7061)	0.800 (1.6649)	0.468 (0.3801)	0.907 (1.2822)
IgA, C3W4	0.721 (0.6355)	0.675 (0.4819)	0.808 (0.7931)	0.977 (0.6458)	0.514 (0.3621)	0.486 (0.3868)
IgG, C3W4	5.925 (3.5059)	5.481 (2.1226)	5.949 (3.4089)	7.232 (4.0103)	5.276 (3.3056)	5.974 (2.7992)
IgM, C3W4	0.692 (1.3420)	0.485 (0.4929)	0.882 (1.9833)	0.429 (0.3497)	0.636 (0.7764)	0.488 (0.4816)
IgA, C7W4	0.793 (0.6608)	0.723 (0.6730)	0.945 (0.6724)	0.725 (0.6011)	0.537 (0.4356)
IgG, C7W4	6.250 (3.5225)	5.817 (3.4944)	7.254 (3.7588)	5.420 (2.2062)	5.135 (2.6309)
IgM, C7W4	0.762 (1.7523)	0.844 (2.1136)	0.414 (0.3400)	1.865 (2.3547)	0.447 (0.4732)
IgA, C9W4	0.719 (0.6336)	0.630 (0.6005)	0.952 (0.6997)	0.567 (0.3968)
IgG, C9W4	6.164 (3.5886)	5.553 (3.0792)	7.768 (4.5126)	5.709 (2.1629)
IgM, C9W4	0.853 (2.3484)	0.973 (2.7574)	0.536 (0.4209)	0.484 (0.4493)
IgA, 6M FU	0.880 (NA)
IgG, 6M FU	8.670 (NA)
IgM, 6M FU	0.200 (NA)
IgA, 9M FU	0.890 (0.0849)	0.510 (0.4585)	0.890 (0.0849)
IgG, 9M FU	7.695 (0.9263)	5.016 (2.4292)	7.695 (0.9263)
IgM, 9M FU	0.375 (0.1061)	0.246 (0.0706)	0.375 (0.1061)
IgA, 12M FU	0.721 (0.8339)	0.983 (0.6029)	0.826 (0.9960)	0.477 (0.1595)	0.300 (0.000)
IgG, 12M FU	6.423 (3.5390)	7.497 (1.5550)	7.621 (3.3834)	3.627 (2.2938)	4.935 (0.8273)
IgM, 12M FU	0.384 (0.3463)	0.487 (0.2743)	0.3334 (0.2833)	0.500 (0.5197)	0.240 (0.0566)
IgA, 18M FU	0.520 (0.2803)	1.095 (0.2616)	0.500 (0.2965)	0.660 (NA)	0.300 (0.000)
IgG, 18M FU	4.513 (2.0789)	6.620 (2.3759)	4.206 (2.0405)	6.660 (NA)	4.265 (1.1384)
IgM, 18M FU	0.417 (3.3156)	0.640 (0.2687)	0.317 (0.1490)	1.120 (NA)	0.240 (0.0566)
IgA, 24M FU	0.540 (0.2667)	1.540 (NA)	0.480 (0.2662)	0.780 (NA)
IgG, 24M FU	5.634 (2.4734)	10.900 (NA)	5.098 (2.4977)	7.780 (NA)
IgM, 24M FU	0.490 (0.3621)	1.710 (NA)	0.333 (0.0971)	1.120 (NA)
IgA, 30M FU	0.505 (0.2900)	1.380 (NA)	0.505 (0.2900)
IgG, 30M FU	3.460 (1.8809)	11.100 (NA)	3.460 (1.8809)
IgM, 30M FU	0.400 (0.1131)	0.770 (NA)	0.400 (0.1131)
IgA, 36M FU	0.550 (0.3111)	1.680 (NA)	0.550 (0.3111)
IgG, 36M FU	4.320 (2.2486)	13.600 (NA)	4.320 (2.2486)
IgM, 36M FU	1.175 (0.2899)	0.720 (NA)	1.175 (0.2899)
IgA, 42M FU	0.545 (0.2051)	1.410 (NA)	0.545 (0.2051)
IgG, 42M FU	4.425 (3.5143)	11.500 (NA)	4.425 (3.5143)
IgM, 42M FU	2.155 (0.8697)	0.470 (NA)	2.155 (0.8697)

13. Secondary Outcome

Title	Number of Participants Who Were Positive or Negative for Human Anti-Human Antibodies (HAHA) Post-OFA Therapy
Description	The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. All samples were first assessed in a screening (SCR) assay, and the potential positive (Pos) samples were further tested in the confirmation (CNF) assays. Confirmed positives were reported as HAHA positive and titer was determined for each positive sample. The drug tolerance of the HAHA assay is 200 microgram/milliliter (µg/mL); thus, samples that tested negative in the assay and had ofatumumab concentrations no more than 200 µg/mL were considered as conclusive negative (Neg) results.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with post-OFA treatment HAHA results were analyzed.

Arm/Group Title	Any Ofatumumab (OFA)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)	OFA Salvage
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	The participants in this arm are from the Physician's Choice (PC) arm. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	78	24	13	41	22
CNF Pos	0 0%	0 0%	0 0%	0 0%	0 0%
Neg and no OFA concentration <200 ug/mL	12 15.2%	1 2.3%	1 4.2%	10 76.9%	4 9.5%
Neg and at least one OFA concentration <200 ug/mL	57 72.2%	23 53.5%	12 50%	22 169.2%	15 35.7%

14. Secondary Outcome

Title	Changes From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)
Description	The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales - fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection (4 items) - and single item scales (social activities [Social Problems (SP) Scale] and future health worries[Future Health (FH) Scale].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 - 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Week (W) 12 (W4 of Cycle[C] 3), W24 (W4C6), W36 (W4C9), W48 (W4C13); during Follow-up which was every month for Months (M) 1-6, every 8 weeks for M7-12 and every 3 months up to M60; and then at PD.
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all participants who were randomised to receive OFA or PC at the first randomisation.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13
DES, C3W4	-10.3 (17.60)	-6.3 (16.22)	-9.7 (12.20)	-10.4 (17.09)
DES, C6W4	-8.5 (15.82)	-6.4 (16.37)	-8.3 (14.95)	-9.8 (18.19)
DES, C9W4	-11 (17.72)	-7.5 (17.91)	-19.8 (14.73)
DES, C12W4	-3.3 (21.78)	-3.3 (21.78)
DES, 5MFU	0 (NA)
DES, 6MFU	0 (NA)
DES, 7MFU	-14.6 (16.52)
DES, 9MFU	0 (23.57)	-9.7 (9.74)	0 (23.57)
DES, 11MFU	-25 (NA)	-6.7 (18.07)	-25 (NA)
DES, 12MFU	-10.8 (14.19)	-2.8 (20.97)	-10.4 (14.6)	-12.5 (17.68)
DES, 15MFU	-4.8 (13.49)	-5.6 (17.35)	-4.8 (13.49)
DES, 18MFU	-3.3 (13.94)	-20.8 (17.68)	-3.3 (13.94)
DES, 21MFU	5.6 (20.97)	-12.5 (5.89)	5.6 (20.97)
DES, 24MFU	4.2 (5.89)	0 (NA)	4.2 (5.89)
DES, 27MFU	0 (NA)	0 (NA)
DES, 30MFU	0 (NA)	0 (NA)
Fatigue Scale, C3W4	-4 (24.04)	2.4 (21.91)	-2.1 (19.23)	-12.5 (24.75)
Fatigue Scale, C6W4	-5.7 (19.99)	12.8 (29.78)	-0.7 (16.65)	-13.6 (19.46)
Fatigue Scale, C9W4	-4.2 (25.1)	0 (24.78)	-14.6 (24.3)
Fatigue Scale, C12W4	7.8 (33.85)	7.8 (33.85)
Fatigue Scale, 5MFU	16.7 (NA)
Fatigue Scale, 6MFU	16.7 (NA)
Fatigue Scale, 7MFU	-14.6 (18.77)
Fatigue Scale, 9MFU	41.7 (82.5)	-8.3 (22.97)	41.7 (82.5)
Fatigue Scale, 11MFU	16.7 (NA)	-6.7 (19)	-16.7 (NA)
Fatigue Scale,12MFU	5 (20.86)	-22.2 (9.62)	6.3 (21.71)	0 (23.57)
Fatigue Scale, 15MFU	2.4 (22.42)	0 (16.67)	2.4 (22.42)
Fatigue Scale, 18MFU	3.3 (21.73)	0 (0)	3.3 (21.73)
Fatigue Scale, 21MFU	16.7 (28.87)	0 (23.57)	16.7 (28.87)
Fatigue Scale, 24MFU	41.7 (58.93)	16.7 (NA)	41.7 (58.93)
Fatigue Scale, 27MFU	0 (NA)	0 (NA)
Fatigue Scale, 30MFU	0 (NA)	0 (NA)
Future Health Scale, C3W4	-6.9 (27.04)	-7.9 (31.46)	-4.2 (22.66)	-6.1 (29.13)
Future Health Scale, C6W4	-12.9 (29.83)	-5.1 (18.49)	-11.1 (25.38)	-24.2 (39.7)
Future Health Scale, C9W4	-14.3 (27.86)	-11.7 (27.09)	-20.8 (30.54)
Future Health Scale, C12W4	-4.4 (39.57)	-4.4 (39.57)
Future Health Scale, 5MFU	0 (NA)
Future Health Scale, 6MFU	33.3 (NA)
Future Health Scale, 7MFU	-12.5 (24.8)
Future Health Scale, 9MFU	0 (47.14)	-22.2 (40.37)	0 (47.14)
Future Health Scale, 11MFU	0 (NA)	-13.3 (18.26)	0 (NA)
Future Health Scale, 12MFU	-10 (31.62)	-11.1 (19.25)	-4.2 (33.03)	-33.3 (0)
Future Health Scale, 15MFU	19 (17.82)	-11.1 (19.25)	19 (17.82)
Future Health Scale, 18MFU	20 (18.26)	-16.7 (23.57)	20 (18.26)
Future Health Scale, 21MFU	22.2 (19.25)	-16.7 (23.57)	22.2 (19.25)
Future Health Scale, 24MFU	33.3 (47.14)	0 (NA)	33.3 (47.14)
Future Health Scale, 27MFU	0 (NA)	0 (NA)
Future Health Scale, 30MFU	0 (NA)	0 (NA)
Infection Scale, C3W4	2.1 (23.6)	3.2 (19.63)	-1 (20.01)	-5.6 (12.48)
Infection Scale, C6W4	-3.7 (22.66)	12.2 (25.6)	-5.6 (19.91)	-6.8 (19.3)
Infection Scale,C9W4	-7.4 (18.61)	-7.5 (16.86)	-7.3 (23.75)
Infection Scale, C12W4	-11.7 (14.02)	-11.7 (14.02)
Infection Scale, 5MFU	0 (NA)
Infection Scale, 6MFU	8.3 (NA)
Infection Scale, 7MFU	-9.4 (12.15)
Infection Scale, 9MFU	16.7 (23.57)	0 (13.94)	16.7 (23.57)
Infection Scale, 11MFU	0 (NA)	-6.7 (12.36)	0 (NA)
Infection Scale, 12MFU	-7.5 (20.58)	2.8 (12.73)	-6.2 (20.29)	-12.5 (29.46)
Infection Scale, 15MFU	-2.4 (17.82)	-2.8 (20.97)	-2.4 (17.82)
Infection Scale, 18MFU	5 (12.64)	-8.3 (11.79)	5 (12.64)
Infection Scale, 21MFU	2.8 (12.73)	8.3 (0)	2.8 (12.73)
Infection Scale, 24MFU	0 (0)	8.3 (NA)	0 (0)
Infection Scale, 27MFU	0 (NA)	0 (NA)
Infection Scale, 30MFU	0 (NA)	0 (NA)
SP Scale, C3W4	-9 (27.56)	3.2 (36.37)	-11.1 (23.4)	-13.9 (30.01)
SP Scale, C6W4	-10.6 (27.63)	10.3 (31.58)	-9.7 (25.02)	-15.2 (31.14)
SP Scale, C9W4	-13.1 (27.72)	-11.7 (29.17)	-16.7 (25.2)
SP Scale, C12W4	-11.1 (37.09)	-11.1 (37.09)
SP Scale, 5MFU	-33.3 (NA)
SP Scale, 6MFU	-66.7 (NA)
SP Scale, 7MFU	-16.7 (25.2)
SP Scale, 9MFU	16.7 (70.71)	-5.6 (32.77)	16.7 (70.71)
SP Scale, 11MFU	-33.3 (NA)	-6.7 (36.51)	-33.3 (NA)
SP Scale, 12MFU	-16.7 (23.57)	-22.2 (19.25)	-16.7 (25.2)	-16.7 (23.57)
SP Scale, 15MFU	-9.5 (37.09)	-11.1 (19.25)	-9.5 (37.09)
SP Scale, 18MFU	0 (23.57)	-16.7 (23.57)	0 (23.57)
SP Scale, 21MFU	-22.2 (38.49)	-16.7 (23.57)	-22.2 (38.49)
SP Scale, 24MFU	33.3 (47.14)	0 (NA)	33.3 (47.14)
SP Scale, 27MFU	0 (NA)	NA (NA)	0 (NA)
SP Scale, 30MFU	0 (NA)	0 (NA)
TSE Scale, C3W4	-4.8 (15.33)	-1.5 (16.82)	-2.4 (10.85)	-8.3 (13.76)
TSE Scale, C6W4	-4.2 (14.33)	3.2 (12.52)	-0.2 (11.32)	-9.1 (16.44)
TSE Scale, C9W4	-5.4 (15.75)	-3.7 (13.91)	-9.4 (20.14)
TSE Scale, C12W4	-2.8 (14.66)	-2.8 (14.66)
TSE Scale, 5MFU	16.7 (NA)
TSE Scale, 6MFU	16.7 (NA)
TSE Scale, 7MFU	-8.3 (17.82)
TSE Scale, 9MFU	8.3 (11.79)	-1.4 (9.74)	8.3 (11.79)
TSE Scale, 11MFU	0 (NA)	-1.7 (14.91)	0 (NA)
TSE Scale, 12MFU	-4.2 (19.74)	2.8 (12.73)	0 (12.6)	-20.8 (41.25)
TSE Scale, 15MFU	-8.3 (12.73)	2.8 (9.62)	-8.3 (12.73)
TSE Scale, 18MFU	6.7 (16.03)	0 (11.79)	6.7 (16.03)
TSE Scale, 21MFU	8.3 (22.05)	0 (0)	8.3 (22.05)
TSE Scale, 24MFU	4.2 (5.89)	0 (NA)	4.2 (5.89)
TSE Scale, 27MFU	8.3 (NA)	8.3 (NA)
TSE Scale, 30MFU	0 (NA)	0 (NA)

15. Secondary Outcome

Title	Mean Health Change Questionnaire (HCQ) Score
Description	The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. A score of 3 or less indicates improvement from Baseline. HCQ was assessed at Screening; Week (W) 12 (W4 of Cycle[C] 3), W24 (W4C6), W36 (W4C9), W48 (W4C13); during follow-up which was every month for Months 1-6, every 8 weeks for M7-12 and every 3 months up to M60; and then at PD..
Time Frame	From the randomization date up to 60 months post the randomization date.

Outcome Measure Data

Analysis Population Description

Population Description: Intent-to-treat (ITT) population: all participants who were randomised to receive OFA or PC at the first randomisation.

Arm/Group Title	Any Ofatumumab (OFA)	Physician's Choice (PC)	Ofatumumab Extended (OFA Ext)	Ofatumumab Observation (OFA Observ.)	OFA First Randomization Only (OFA FRO)	OFA Salvage
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.	Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.	The participants in this arm are from the Physician's Choice (PC) arm. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU.
Measure Participants	79	43	24	13	42	22
C3W4	2.8 (1.57)	3.9 (2.01)	2.5 (1.44)	2.8 (0.97)	3.2 (1.90)	3.1 (1.92)
C6W4	3.2 (2.04)	3.5 (2.37)	2.7 (1.66)	2.9 (1.76)	5.1 (2.37)	3.0 (2.00)
C9W4	2.8 (1.60)	2.5 (1.36)	3.5 (2.00)	3.1 (2.48)
C12W4	2.6 (1.99)	2.6 (1.99)	3.0 (1.83)
3MFU	3.0 (NA)
5MFU	5.0 (NA)
6MFU	3.0 (NA)
7MFU	2.4 (1.30)
9MFU	6.5 (2.12)	3.5 (2.07)	6.5 (2.12)
11MFU	5.0 (NA)	3.0 (2.35)	5.0 (NA)
12MFU	3.4 (2.07)	2.3 (1.53)	3.5 (2.27)	3.0 (1.41)	2.0 (1.41)
15MFU	3.5 (2.27)	3.7 (1.53)	3.7 (2.35)	2.0 (NA)	2.0 (1.00)
18MFU	2.6 (2.15)	4.5 (0.71)	2.8 (2.23)	1.0 (NA)	4.0 (4.24)
21MFU	2.0 (1.22)	6.0 (1.41)	2.3 (1.26)	1.0 (NA)
24MFU	2.5 (3.00)	4.0 (NA)	3.0 (3.46)	1.0 (NA)
27MFU	2.7 (2.89)	5.0 (NA)	3.5 (3.54)	1.0 (NA)
30MFU	1.0 (NA)	5.0 (NA)	1.0 (NA)
33MFU	3.0 (2.83)	5.0 (NA)	3.0 (2.83)
36MFU	3.0 (2.83)	5.0 (NA)	3.0 (2.83)
39MFU	4.0 (4.24)	7.0 (NA)	4.0 (4.24)
42MFU	3.0 (2.83)	5.0 (NA)	3.0 (2.83)
45MFU	1.0 (NA)	7.0 (NA)	1.0 (NA)

Adverse Events

Time Frame	SAEs & AEs were collected from first dose of study medication to 60 days after last dose of study medication & until end of the follow-up period (60 months post the randomization date) for SAEs unless initiation of subsequent anti-CLL therapy. AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit
Arm/Group Title	Any Ofatumumab		Ofatumumab Extended		Ofatumumab Observation		Ofatumumab		Physicians Choice		Ofatumumab Salvage
Arm/Group Description	Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.		Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.		Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.		Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.		Par. randomized to receive PC trt during Randomization 1 were administered treatments approved for Chronic Lymphocytic Leukaemia (CLL) and well established standards of care as prescribed with standard dose and route. Experimental therapies or any doses beyond the approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive s(ingleagent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU. Par. who did not receive OFA salvage trt and demonstrated PD, entered SFU		Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anticancer therapy information was collected in the SFU.
All Cause Mortality
	Any Ofatumumab		Ofatumumab Extended		Ofatumumab Observation		Ofatumumab		Physicians Choice		Ofatumumab Salvage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/78 (20.5%)		2/24 (8.3%)		3/13 (23.1%)		11/41 (26.8%)		8/43 (18.6%)		5/22 (22.7%)
Serious Adverse Events
	Any Ofatumumab		Ofatumumab Extended		Ofatumumab Observation		Ofatumumab		Physicians Choice		Ofatumumab Salvage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/78 (55.1%)		12/24 (50%)		5/13 (38.5%)		26/41 (63.4%)		23/43 (53.5%)		10/22 (45.5%)
Blood and lymphatic system disorders
Anaemia	2/78 (2.6%)		0/24 (0%)		1/13 (7.7%)		1/41 (2.4%)		4/43 (9.3%)		2/22 (9.1%)
Autoimmune haemolytic anaemia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		2/43 (4.7%)		1/22 (4.5%)
Febrile neutropenia	7/78 (9%)		0/24 (0%)		1/13 (7.7%)		6/41 (14.6%)		4/43 (9.3%)		1/22 (4.5%)
Haemolytic anaemia	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Leukopenia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Neutropenia	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Thrombocytopenia	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Cardiac disorders
Atrial fibrillation	2/78 (2.6%)		0/24 (0%)		0/13 (0%)		2/41 (4.9%)		1/43 (2.3%)		0/22 (0%)
Cardiac arrest	2/78 (2.6%)		0/24 (0%)		0/13 (0%)		2/41 (4.9%)		0/43 (0%)		0/22 (0%)
Cardiac failure	2/78 (2.6%)		1/24 (4.2%)		0/13 (0%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Cardiac failure acute	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		2/22 (9.1%)
Cardiovascular insufficiency	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Coronary artery insufficiency	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Myocardial infarction	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Supraventricular tachycardia	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Ventricular tachycardia	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Endocrine disorders
Hypercalcaemia of malignancy	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Eye disorders
Chorioretinal atrophy	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Gastrointestinal disorders
Abdominal pain	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Diarrhoea	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Diverticulum intestinal haemorrhagic	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
General disorders
Chills	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Death	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
General physical health deterioration	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Multiple organ dysfunction syndrome	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Oedema peripheral	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Pyrexia	4/78 (5.1%)		0/24 (0%)		0/13 (0%)		4/41 (9.8%)		3/43 (7%)		2/22 (9.1%)
Hepatobiliary disorders
Cholelithiasis	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Drug-induced liver injury	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Hepatitis toxic	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Hepatotoxicity	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Infections and infestations
Abscess neck	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Acute sinusitis	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Atypical pneumonia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Bronchitis	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Bronchopulmonary aspergillosis	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Cellulitis	2/78 (2.6%)		1/24 (4.2%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Device related infection	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Empyema	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Enterocolitis infectious	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Gastrointestinal fungal infection	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Hepatitis B	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Hepatitis E	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Lower respiratory tract infection	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Lung infection	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Meningitis	2/78 (2.6%)		1/24 (4.2%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Meningitis aseptic	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Neutropenic sepsis	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		2/43 (4.7%)		0/22 (0%)
Otosalpingitis	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Pneumonia	10/78 (12.8%)		3/24 (12.5%)		1/13 (7.7%)		6/41 (14.6%)		7/43 (16.3%)		3/22 (13.6%)
Progressive multifocal leukoencephalopathy	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Pseudomembranous colitis	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Sepsis	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		4/43 (9.3%)		2/22 (9.1%)
Skin infection	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Upper respiratory tract infection	3/78 (3.8%)		1/24 (4.2%)		1/13 (7.7%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Urinary tract infection	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Viral infection	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		1/22 (4.5%)
Viral tonsillitis	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Injury, poisoning and procedural complications
Hip fracture	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Overdose	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Thoracic vertebral fracture	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Investigations
Blood pressure decreased	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
C-reactive protein increased	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Hyperkalaemia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Hypoalbuminaemia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Malnutrition	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Tumour lysis syndrome	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large cell lung cancer	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Oesophageal carcinoma	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Nervous system disorders
Chorea	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Seizure	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Renal and urinary disorders
Acute kidney injury	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Hydronephrosis	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Renal failure	2/78 (2.6%)		0/24 (0%)		0/13 (0%)		2/41 (4.9%)		1/43 (2.3%)		1/22 (4.5%)
Renal impairment	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Urinary retention	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Bronchospasm	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Chronic obstructive pulmonary disease	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Dyspnoea	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Epistaxis	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Hydrothorax	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Lung disorder	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Lung infiltration	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Obstructive airways disorder	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Pleural effusion	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Pneumonitis	2/78 (2.6%)		1/24 (4.2%)		0/13 (0%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Pulmonary embolism	1/78 (1.3%)		1/24 (4.2%)		0/13 (0%)		0/41 (0%)		0/43 (0%)		1/22 (4.5%)
Pulmonary oedema	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Vascular disorders
Hypotension	2/78 (2.6%)		0/24 (0%)		0/13 (0%)		2/41 (4.9%)		0/43 (0%)		0/22 (0%)
Thrombophlebitis	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Any Ofatumumab		Ofatumumab Extended		Ofatumumab Observation		Ofatumumab		Physicians Choice		Ofatumumab Salvage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/78 (80.8%)		20/24 (83.3%)		10/13 (76.9%)		33/41 (80.5%)		30/43 (69.8%)		13/22 (59.1%)
Blood and lymphatic system disorders
Anaemia	5/78 (6.4%)		2/24 (8.3%)		0/13 (0%)		3/41 (7.3%)		5/43 (11.6%)		1/22 (4.5%)
Leukopenia	2/78 (2.6%)		0/24 (0%)		1/13 (7.7%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Lymphocytosis	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Neutropenia	15/78 (19.2%)		10/24 (41.7%)		1/13 (7.7%)		4/41 (9.8%)		8/43 (18.6%)		3/22 (13.6%)
Thrombocytopenia	8/78 (10.3%)		3/24 (12.5%)		1/13 (7.7%)		4/41 (9.8%)		3/43 (7%)		1/22 (4.5%)
Cardiac disorders
Cardiac failure	3/78 (3.8%)		2/24 (8.3%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Ear and labyrinth disorders
Ear congestion	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Hypoacusis	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Vertigo	2/78 (2.6%)		1/24 (4.2%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Eye disorders
Visual impairment	2/78 (2.6%)		0/24 (0%)		1/13 (7.7%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Gastrointestinal disorders
Abdominal pain upper	4/78 (5.1%)		2/24 (8.3%)		0/13 (0%)		2/41 (4.9%)		1/43 (2.3%)		0/22 (0%)
Constipation	3/78 (3.8%)		1/24 (4.2%)		1/13 (7.7%)		1/41 (2.4%)		1/43 (2.3%)		1/22 (4.5%)
Diarrhoea	5/78 (6.4%)		0/24 (0%)		0/13 (0%)		5/41 (12.2%)		4/43 (9.3%)		2/22 (9.1%)
Nausea	8/78 (10.3%)		2/24 (8.3%)		1/13 (7.7%)		5/41 (12.2%)		5/43 (11.6%)		1/22 (4.5%)
Vomiting	4/78 (5.1%)		0/24 (0%)		0/13 (0%)		4/41 (9.8%)		3/43 (7%)		0/22 (0%)
General disorders
Asthenia	3/78 (3.8%)		0/24 (0%)		0/13 (0%)		3/41 (7.3%)		0/43 (0%)		0/22 (0%)
Chills	9/78 (11.5%)		1/24 (4.2%)		2/13 (15.4%)		6/41 (14.6%)		1/43 (2.3%)		0/22 (0%)
Fatigue	3/78 (3.8%)		0/24 (0%)		1/13 (7.7%)		2/41 (4.9%)		4/43 (9.3%)		0/22 (0%)
Oedema peripheral	2/78 (2.6%)		0/24 (0%)		1/13 (7.7%)		1/41 (2.4%)		3/43 (7%)		0/22 (0%)
Peripheral swelling	4/78 (5.1%)		1/24 (4.2%)		0/13 (0%)		3/41 (7.3%)		1/43 (2.3%)		0/22 (0%)
Pyrexia	8/78 (10.3%)		2/24 (8.3%)		1/13 (7.7%)		5/41 (12.2%)		3/43 (7%)		2/22 (9.1%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Infections and infestations
Bronchitis	7/78 (9%)		5/24 (20.8%)		0/13 (0%)		2/41 (4.9%)		3/43 (7%)		1/22 (4.5%)
Cytomegalovirus infection	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		4/43 (9.3%)		0/22 (0%)
Eye infection	2/78 (2.6%)		0/24 (0%)		1/13 (7.7%)		1/41 (2.4%)		0/43 (0%)		1/22 (4.5%)
Fungal infection	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Gastroenteritis	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Herpes virus infection	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Laryngitis	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Nasopharyngitis	5/78 (6.4%)		3/24 (12.5%)		1/13 (7.7%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Pneumonia	4/78 (5.1%)		3/24 (12.5%)		0/13 (0%)		1/41 (2.4%)		1/43 (2.3%)		0/22 (0%)
Respiratory tract infection	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Sialoadenitis	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Sinusitis	4/78 (5.1%)		2/24 (8.3%)		1/13 (7.7%)		1/41 (2.4%)		2/43 (4.7%)		1/22 (4.5%)
Tracheitis	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Upper respiratory tract infection	4/78 (5.1%)		0/24 (0%)		2/13 (15.4%)		2/41 (4.9%)		5/43 (11.6%)		2/22 (9.1%)
Urinary tract infection	3/78 (3.8%)		0/24 (0%)		0/13 (0%)		3/41 (7.3%)		1/43 (2.3%)		0/22 (0%)
Injury, poisoning and procedural complications
Arthropod bite	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Contusion	3/78 (3.8%)		2/24 (8.3%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Investigations
Alanine aminotransferase increased	4/78 (5.1%)		1/24 (4.2%)		1/13 (7.7%)		2/41 (4.9%)		1/43 (2.3%)		1/22 (4.5%)
Aspartate aminotransferase increased	3/78 (3.8%)		1/24 (4.2%)		1/13 (7.7%)		1/41 (2.4%)		0/43 (0%)		1/22 (4.5%)
Blood bilirubin increased	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Haemoglobin decreased	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Lymphocyte count decreased	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Neutrophil count decreased	2/78 (2.6%)		1/24 (4.2%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Weight decreased	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		2/43 (4.7%)		2/22 (9.1%)
Weight increased	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		1/22 (4.5%)
Metabolism and nutrition disorders
Hypercalcaemia	3/78 (3.8%)		0/24 (0%)		0/13 (0%)		3/41 (7.3%)		0/43 (0%)		0/22 (0%)
Hyperglycaemia	0/78 (0%)		0/24 (0%)		0/13 (0%)		0/41 (0%)		1/43 (2.3%)		2/22 (9.1%)
Hyperkalaemia	4/78 (5.1%)		1/24 (4.2%)		0/13 (0%)		3/41 (7.3%)		0/43 (0%)		0/22 (0%)
Hyperuricaemia	2/78 (2.6%)		2/24 (8.3%)		0/13 (0%)		0/41 (0%)		2/43 (4.7%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/78 (2.6%)		0/24 (0%)		2/13 (15.4%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Back pain	4/78 (5.1%)		1/24 (4.2%)		0/13 (0%)		3/41 (7.3%)		1/43 (2.3%)		1/22 (4.5%)
Intervertebral disc disorder	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Nervous system disorders
Dizziness	1/78 (1.3%)		0/24 (0%)		0/13 (0%)		1/41 (2.4%)		0/43 (0%)		2/22 (9.1%)
Headache	3/78 (3.8%)		0/24 (0%)		0/13 (0%)		3/41 (7.3%)		0/43 (0%)		0/22 (0%)
Hypoaesthesia	2/78 (2.6%)		0/24 (0%)		1/13 (7.7%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Muscle spasticity	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Paraesthesia	3/78 (3.8%)		0/24 (0%)		1/13 (7.7%)		2/41 (4.9%)		0/43 (0%)		0/22 (0%)
Psychiatric disorders
Depressed mood	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Reproductive system and breast disorders
Erectile dysfunction	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	11/78 (14.1%)		3/24 (12.5%)		2/13 (15.4%)		6/41 (14.6%)		1/43 (2.3%)		2/22 (9.1%)
Dyspnoea	3/78 (3.8%)		1/24 (4.2%)		1/13 (7.7%)		1/41 (2.4%)		2/43 (4.7%)		1/22 (4.5%)
Nasal obstruction	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		0/43 (0%)		0/22 (0%)
Productive cough	4/78 (5.1%)		0/24 (0%)		2/13 (15.4%)		2/41 (4.9%)		0/43 (0%)		1/22 (4.5%)
Skin and subcutaneous tissue disorders
Dry skin	3/78 (3.8%)		1/24 (4.2%)		1/13 (7.7%)		1/41 (2.4%)		0/43 (0%)		0/22 (0%)
Pruritus	5/78 (6.4%)		0/24 (0%)		0/13 (0%)		5/41 (12.2%)		2/43 (4.7%)		0/22 (0%)
Rash	3/78 (3.8%)		1/24 (4.2%)		1/13 (7.7%)		1/41 (2.4%)		2/43 (4.7%)		2/22 (9.1%)
Skin lesion	1/78 (1.3%)		0/24 (0%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Urticaria	3/78 (3.8%)		2/24 (8.3%)		1/13 (7.7%)		0/41 (0%)		1/43 (2.3%)		0/22 (0%)
Vascular disorders
Flushing	3/78 (3.8%)		0/24 (0%)		1/13 (7.7%)		2/41 (4.9%)		0/43 (0%)		0/22 (0%)
Hypertension	5/78 (6.4%)		2/24 (8.3%)		0/13 (0%)		3/41 (7.3%)		0/43 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.