PROLONG: Ofatumumab Maintenance Treatment vs No Further Treatment in Relapsed CLL Responding to Induction Therapy

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT01039376

Collaborator

(none)

480

Enrollment

203

Locations

Arms

97.7

Actual Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to determine if maintenance therapy with ofatumumab would prolong remission in patients with CLL who have responded to second or third line treatment. This study would also evaluate the safety of ofatumumab maintenance compared to observation (the current standard of care). This study was co-developed with the HOVON and NORDIC CLL group and would be conducted as a collaborative effort with GSK.

Condition or Disease	Intervention/Treatment	Phase
Leukaemia, Lymphocytic, Chronic	Biological: Ofatumumab Other: Observation	Phase 3

Detailed Description

The study met its primary objective at the protocol defined interim analysis (data cut-off 19-Jun-2014). The protocol-defined final analysis of the primary endpoint was performed when 280 PFS events were reached (data cut-off 20-Feb-2017).

Study Design

Study Type:

Interventional

Actual Enrollment :

480 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Maintenance Treatment Versus no Further Treatment in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL) Who Have Responded to Induction Therapy

Actual Study Start Date :

May 6, 2010

Actual Primary Completion Date :

Feb 20, 2017

Actual Study Completion Date :

Jun 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARM A: Ofatumumab 300 mg IV Week 1 followed by 1000 mg IV Week 2 1000 mg IV (a dose every 8 weeks for up to 2 years following the first 1000 mg dose)	Biological: Ofatumumab Ofatumumab for maintenance therapy as IV infusions every 8 weeks . The first dose was 300 mg followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to 2 years.
Other: ARM B: Observation and assessments as per Arm A Disease status assessments to determine subject response or progression performed approximately every 8 weeks for up to 2 years for both arms according to IWCLL criteria	Other: Observation Observation/Safety Evaluation

Arm

Intervention/Treatment

Experimental: ARM A: Ofatumumab

300 mg IV Week 1 followed by 1000 mg IV Week 2 1000 mg IV (a dose every 8 weeks for up to 2 years following the first 1000 mg dose)

Biological: Ofatumumab

Ofatumumab for maintenance therapy as IV infusions every 8 weeks . The first dose was 300 mg followed 1 week later by 1000 mg and 1000 mg every 8 weeks thereafter for up to 2 years.

Other: ARM B: Observation and assessments as per Arm A

Disease status assessments to determine subject response or progression performed approximately every 8 weeks for up to 2 years for both arms according to IWCLL criteria

Other: Observation

Observation/Safety Evaluation

Outcome Measures

Primary Outcome Measures

Progression-free Survival, as Assessed by the Investigator [From randomization until progression or death (up to 79 months)]
Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the investigator according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [cm]), spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site); an increase by 50% or more in the previously noted enlargement of the liver or spleen; an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter; transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukemia.
Progression-free Survival, as Assessed by the Independent Review Committee (IRC) [From randomization until progression or death (up to 79 months)]
Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the IRC according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [cm]), spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site); an increase by 50% or more in the previously noted enlargement of the liver or spleen; an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter; transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukemia.

Secondary Outcome Measures

Overall Survival [From randomization until death (up to 88 months)]
Overall survival is defined as time from randomization to date of death.
Number of Participants With Improvement in Response From Baseline [From Baseline until the end of the study (up to 88 months)]
Improvement in response was assessed by calculating the percentage of participants who changed from partial response (PR) at Baseline to complete response during the study.
Time to Next Therapy [From randomization until the end of the study (up to 88 months)]
Time to next therapy is defined as the time from randomization to the date of receiving the next CLL treatment.
Progression-free Survival After Next-line Therapy [From randomization until progression or death (up to 88 months)]
Progression-free survival after next-line therapy is defined as the time from randomization until progression or death following the next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy and who did not have progression or death after next-line therapy were censored at their last date of contact. Participant who died prior to next-line therapy, was counted as an event.
Time to Progression After Next-line Therapy [From randomization until progression or death (up to 88 months)]
Time to progression after next-line therapy is defined as the time from progression following randomization until progression or death following next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy with a PD prior to receiving next line therapy and who did not had progression or death after next-line therapy were censored at their last date of contact. If a participant died prior to next-line therapy, this was counted as an event.
Change From Baseline (BL) in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16) [From randomization until the end of the study (up to 47 months)]
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 Likert 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 = severe symptoms or problems. Changes from Baseline were analyzed by a mixed model-repeated measures analysis of covariance (ANCOVA).
Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score [From randomization until the end of the study (up to 47 months)]
The EORTC QLQ-C30 is a self-reported, 30-item cancer-specific instrument that assesses 15 domains: physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items), pain (2 items), fatigue (3 items), nausea and vomiting (2 items), five single-item symptom scores (insomnia, loss of appetite, constipation, diarrhea, and dyspnea), a single item asking about financial difficulties, and global health status/quality of life (QOF) consisting of 2 items. Functional and symptoms scales were measured on a four-point Likert scale, where 1 = not at all and 4 = very much, whereas global health status or QOF was assessed using a 7-item Likert scale, ranging from "poor" (worse quality of life) to "excellent" (better quality of life). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA.
Change From Baseline in the Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale [From screening until the end of the study (up to 47 months)]
EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (worst health) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA. A negative adjusted mean change from Baseline represents a worsening of quality of life.
Number of Participants With an Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the Indicated Time Points [From randomization until the end of the study (up to 88 months)]
Improvement is defined as a decrease from Baseline by at least one step on the ECOG performance status scale (improvement categorized as yes or no). Improvement in ECOG performance status was measured.
Number of Participants With the Indicated Constitutional or B-symptoms at the Indicated Time Points [From Screening until the end of the study (up to 88 months)]
Participants with the indicated constitutional or B-symptoms (night sweats [without signs of infection]; unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of > 38 degrees celcius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue) were presented. The proportion of participants with no night sweats, no weight loss, no fever and no extreme fatigue were summarized.
Number of Participants With Grade 3 and Above Adverse Event of Infection [From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 26 months)]
Participants with Grade 3, Grade 4 and Grade 5 adverse event of infection are presented. Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.0 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death).
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months)]
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Number of Participants With a Grade 3 or Grade 4 Myelosuppression (Anemia, Neutropenia, or Thrombocytopenia) at Indicated Time Points [From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until the end of the study for SAEs (88 months)]
Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Number of participants who reported myelosuppression (anemia [low hemoglobin count], neutropenia [low neutrophil count], and thrombocytopenia [low platelet count]) are presented. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 4.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).
Number of Participants Who Received at Least One Transfusion During the Study [From randomization until the end of the study (up to 88 months)]
Participants who received at least one transfusion (any blood products or blood supportive care product) during the study are presented.
Number of Participants Diagnosed With Autoimmune Hemolytic Anemia (AIHA) [From randomization until the end of the study (up to 88 months)]
AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.
Number of Participants With a Positive Anti-ofatumumab Antibody (Human Anti-human Antibody; HAHA) Result [Pre-dose (Visit 1), Months 7, 13, 19, and 25 during treatment and at 3 and 6 months after last ofatumumab dose (up to 30 months)]
All serum samples for analysis of HAHA were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA positive and further evaluated in the titration test to obtain a titer of HAHA. A confirmed positive result at any time point means the participant is positive for HAHA.Results are reported as the number of participants positive for HAHA.
Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Indicated Time Points [Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 88 months)]
Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-baseline value minus the Baseline value.
Number of Participants Who Were Positive and Negative for Minimal Residual Disease (MRD) at Any Visit [From randomization until the end of the study (up to 88 months)]
MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed complete remission. Number of participants who were positive and negative for minimal residual disease (MRD) at any visit is presented.
Change From Baseline in Cluster of Differentiation (CD) CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points [Baseline and every two months from Month 3 until Month 25 and at every followup (up to 88 months)]
CD5+CD19+ cells were counted by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline CD5+CD19+ and CD5-CD19+ cell count value is the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Summary of Covariates to Compute Cox Proportional Hazards Regression Model for Relationship Between Investigator Assessed Progression-free Survival and the Indicated Prognostic Markers [From Baseline until the end of the study (up to 79 months)]
Blood samples were collected for the assessment of the following prognostic markers at Baseline (BL) and upon relapse: immunoglobulin heavy chain variable region (IgVH) mutational status; VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]) including 6q-, 11q-, +12q, 17p-, 13q- deletions; beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH) at BL, IgVH mutational status at BL, beta 2 microglobulin at BL, BL CD20 and BL complement level. For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=CY G.
Cmax and Ctrough of Ofatumumab [Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)]
Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected at pre-dose and 0.5 hours after the end of the infusion at treatment on Month 1 Week 1 (Day 1), Month 1 Week 2 (Day 8), and at every second infusion.
Total Plasma Clearance (CL) of Ofatumumab [Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)]
Plasma clearance is defined as the plasma volume that is cleared of drug per unit of time.
AUC(0-tau) of Ofatumumab [Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)]
Area under the concentration time curve over the dosing interval (AUC[0-tau]) is a measure of the drug exposure over time.
Vss of Ofatumumab [Day 1 Month 1 ( Cycle 1) through Month 7 ( Cycle 4)]
Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of a drug between plasma and the rest of the body at steady state. Data from all time points collected were used to calculate one Vss value for each individual.
Plasma Half-life (t1/2) of Ofatumumab [Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)]
The terminal half life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original value.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults with documented diagnosis of CLL based on the modified IWCLL updated NCI-WG guidelines (Hallek, 2008)
At least PR according to the revised 2008 NCI-WG CLL criteria, within 3 months of the response assessment after the last dose of 2nd/3rd line treatment
The anti-leukemic treatment before study entry should have been at least 3 months or 3 cycles
ECOG Performance Status of 0-2
Signed written informed consent prior to performing any study-specific procedures

Exclusion Criteria:

Known primary or secondary fludarabine-refractory subjects, defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months
Prior maintenance therapy
Known transformation of CLL (eg.Richter's transformation), prolymphocytic leukemia (PLL), or CNS involvement of CLL
Active Autoimmune hemolytic anemia (AIHA) requiring treatment except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data
Previous autologous or allogeneic stem cell transplantation
Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis B or C
Other past or current malignancy (with the exception of basal cell carcinoma or the skin or in situ carcinoma of the cervix or breasts) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data
Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of exta systoles or minor conduction abnormalities except if in the opinion of the investigator and medical monitor it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data
History of significant cerebrovascular disease or event with symptoms or sequelae
Significant concurrent, uncontrolled medical condition that in the opinion of the investigator or GSK medical monitor contraindicates participation in this study
Other anti-leukemic use of medications including glucocorticoids
Known HIV positive
Screening laboratory values: platelets <50 x 10x9/L, neutrophils<1.0 x 10x9/L, Creatinine > 1.5 X upper normal limit (unless normal creatinine clearance), total bilirubin >1.5 X upper normal limit, ALT >2.5 X upper normal limit (unless due to liver involvement of CLL), alkaline phosphase > 2.5 X upper normal limit
Known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor contraindicates study participation
Subjects who have received treatment with any non-marketed drug substance or experimental therapy within 5-terminal half-lives or 4 weeks whichever is longer prior to first dose of study medication or currently participating in any other interventional clinical study
Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last ofatumumab dose. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is sole partner for that subject. For females in the USA, the use of a double barrier method is also considered adequate (condom or occlusive cap plus spermicidal agent).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Gilbert	Arizona	United States	85234
2	Novartis Investigative Site	Tucson	Arizona	United States	85710
3	Novartis Investigative Site	Tucson	Arizona	United States	85715
4	Novartis Investigative Site	Jonesboro	Arkansas	United States	72401
5	Novartis Investigative Site	Berkeley	California	United States	94704
6	Novartis Investigative Site	La Verne	California	United States	91750
7	Novartis Investigative Site	Sacramento	California	United States	95815
8	Novartis Investigative Site	Sacramento	California	United States	95816
9	Novartis Investigative Site	San Pablo	California	United States	94806
10	Novartis Investigative Site	Hartford	Connecticut	United States	06105
11	Novartis Investigative Site	Gainesville	Florida	United States	32610
12	Novartis Investigative Site	Lake Worth	Florida	United States	33461
13	Novartis Investigative Site	Orlando	Florida	United States	32806
14	Novartis Investigative Site	Pembroke Pines	Florida	United States	33028
15	Novartis Investigative Site	West Palm Beach	Florida	United States	33401
16	Novartis Investigative Site	Macon	Georgia	United States	31201
17	Novartis Investigative Site	Savannah	Georgia	United States	31405
18	Novartis Investigative Site	Post Falls	Idaho	United States	83854
19	Novartis Investigative Site	Indianapolis	Indiana	United States	46202
20	Novartis Investigative Site	Iowa City	Iowa	United States	52242
21	Novartis Investigative Site	Westwood	Kansas	United States	66205
22	Novartis Investigative Site	Metairie	Louisiana	United States	70006
23	Novartis Investigative Site	Cumberland	Maryland	United States	21502
24	Novartis Investigative Site	Hagerstown	Maryland	United States	21742
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31	Novartis Investigative Site	Albuquerque	New Mexico	United States	87110
32	Novartis Investigative Site	Albuquerque	New Mexico	United States	87131
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43	Novartis Investigative Site	Salt Lake City	Utah	United States	84106
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46	Novartis Investigative Site	Derqui, Pilar	Buenos Aires	Argentina	B1629AHJ
47	Novartis Investigative Site	La Plata	Buenos Aires	Argentina	B1900AXI
48	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000KZE
49	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires		Argentina	1114
50	Novartis Investigative Site	Darlinghurst	New South Wales	Australia	2010
51	Novartis Investigative Site	Randwick	New South Wales	Australia	2031
52	Novartis Investigative Site	Clayton	Victoria	Australia	3168
53	Novartis Investigative Site	East Melbourne	Victoria	Australia	3002
54	Novartis Investigative Site	Parkville	Victoria	Australia	3050
55	Novartis Investigative Site	Antwerpen		Belgium	2020
56	Novartis Investigative Site	Antwerpen		Belgium	2060
57	Novartis Investigative Site	Brugge		Belgium	8000
58	Novartis Investigative Site	Brussels		Belgium	1090
59	Novartis Investigative Site	Gent		Belgium	9000
60	Novartis Investigative Site	Hasselt		Belgium	3500
61	Novartis Investigative Site	Roeselare		Belgium	8800
62	Novartis Investigative Site	Wilrijk		Belgium	2610
63	Novartis Investigative Site	Salvador	Bahía	Brazil	41253-190
64	Novartis Investigative Site	Goiania - GO	Goiás	Brazil	74605-020
65	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90610000
66	Novartis Investigative Site	Barretos	São Paulo	Brazil	14784-400
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68	Novartis Investigative Site	Sao Paulo	São Paulo	Brazil	05403-000
69	Novartis Investigative Site	Calgary	Alberta	Canada	T2N 4N2
70	Novartis Investigative Site	Kitchener	Ontario	Canada	N2G 1G3
71	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
72	Novartis Investigative Site	Montreal	Quebec	Canada	H2L 4M1
73	Novartis Investigative Site	Montreal	Quebec	Canada	H3A1A1
74	Novartis Investigative Site	Sherbrooke	Quebec	Canada	J1H 5N4
75	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7N 4H4
76	Novartis Investigative Site	Brno		Czechia	625 00
77	Novartis Investigative Site	Hradec Kralove		Czechia
78	Novartis Investigative Site	Olomouc		Czechia	775 20
79	Novartis Investigative Site	Pelhrimov		Czechia	393 38
80	Novartis Investigative Site	Praha 10		Czechia	100 34
81	Novartis Investigative Site	Herlev		Denmark	2730
82	Novartis Investigative Site	Kobenhavn		Denmark	2100
83	Novartis Investigative Site	Roskilde		Denmark	4000
84	Novartis Investigative Site	Helsinki		Finland	00029
85	Novartis Investigative Site	Jyvaskyla		Finland	40620
86	Novartis Investigative Site	Pori		Finland	28500
87	Novartis Investigative Site	Tampere		Finland	33520
88	Novartis Investigative Site	Turku		Finland	20520
89	Novartis Investigative Site	Blois cedex		France	41016
90	Novartis Investigative Site	Caen cedex 5		France	14076
91	Novartis Investigative Site	Clermont-Ferrand Cedex 1		France	63003
92	Novartis Investigative Site	Dijon		France	21000
93	Novartis Investigative Site	Lille cedex		France	59037
94	Novartis Investigative Site	Marseille Cedex 9		France	13273
95	Novartis Investigative Site	Mulhouse		France	68070
96	Novartis Investigative Site	Pessac cedex		France	33604
97	Novartis Investigative Site	Saint Pierre cedex		France	97448
98	Novartis Investigative Site	Strasbourg cedex		France	67098
99	Novartis Investigative Site	Toulouse cedex 9		France	31059
100	Novartis Investigative Site	Vandoeuvre-Les-Nancy		France	54511
101	Novartis Investigative Site	Athens,		Greece	11 527
102	Novartis Investigative Site	Athens		Greece	115 27
103	Novartis Investigative Site	Piraeus		Greece	18537
104	Novartis Investigative Site	Thessaloniki		Greece	564 29
105	Novartis Investigative Site	Thessaloniki		Greece	57010
106	Novartis Investigative Site	Budapest		Hungary	1097
107	Novartis Investigative Site	Debrecen		Hungary	4012
108	Novartis Investigative Site	Kecskemet		Hungary	6000
109	Novartis Investigative Site	Szeged		Hungary	6725
110	Novartis Investigative Site	Ahmedabad		India	380009
111	Novartis Investigative Site	Mumbai		India	400 012
112	Novartis Investigative Site	Mumbai		India	400014
113	Novartis Investigative Site	Pune		India	411001
114	Novartis Investigative Site	Afula		Israel	18101
115	Novartis Investigative Site	Haifa		Israel	31048
116	Novartis Investigative Site	Haifa		Israel	31096
117	Novartis Investigative Site	Jerusalem		Israel	91031
118	Novartis Investigative Site	Jerusalem		Israel	91120
119	Novartis Investigative Site	Kfar Saba		Israel	44281
120	Novartis Investigative Site	Nahariya		Israel	22100
121	Novartis Investigative Site	Petach-Tikva		Israel	49100
122	Novartis Investigative Site	Ramat Gan		Israel	52621
123	Novartis Investigative Site	Rehovot		Israel	76100
124	Novartis Investigative Site	Tel-Aviv		Israel
125	Novartis Investigative Site	Zrifin		Israel	70300
126	Novartis Investigative Site	Modena	Emilia-Romagna	Italy	41124
127	Novartis Investigative Site	Piacenza	Emilia-Romagna	Italy	29100
128	Novartis Investigative Site	Roma	Lazio	Italy	00144
129	Novartis Investigative Site	Novara	Piemonte	Italy	28100
130	Novartis Investigative Site	Torino	Piemonte	Italy	10126
131	Novartis Investigative Site	Pisa	Toscana	Italy	56100
132	Novartis Investigative Site	Seoul		Korea, Republic of	03080
133	Novartis Investigative Site	Seoul		Korea, Republic of	03722
134	Novartis Investigative Site	Seoul		Korea, Republic of	05505
135	Novartis Investigative Site	Seoul		Korea, Republic of	06351
136	Novartis Investigative Site	Seoul		Korea, Republic of	06591
137	Novartis Investigative Site	Amersfoort		Netherlands	3813 TZ
138	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
139	Novartis Investigative Site	Amsterdam		Netherlands	1091 AC
140	Novartis Investigative Site	Amsterdam		Netherlands	1105 AZ
141	Novartis Investigative Site	Blaricum		Netherlands	1261 AN
142	Novartis Investigative Site	Breda		Netherlands	4819 EV
143	Novartis Investigative Site	Den Bosch		Netherlands	5223 GZ
144	Novartis Investigative Site	Den Haag		Netherlands	2545AA
145	Novartis Investigative Site	Deventer		Netherlands	7416 SE
146	Novartis Investigative Site	Dordrecht		Netherlands	3318 AT
147	Novartis Investigative Site	Enschede		Netherlands	7511JX
148	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
149	Novartis Investigative Site	Hoofddorp		Netherlands	2134 TM
150	Novartis Investigative Site	Leiden		Netherlands	2333 ZA
151	Novartis Investigative Site	Maastricht		Netherlands	6229 HX
152	Novartis Investigative Site	Rotterdam		Netherlands	3015 CE
153	Novartis Investigative Site	Rotterdam		Netherlands	3075 EA
154	Novartis Investigative Site	Rotterdam		Netherlands	3079 DZ
155	Novartis Investigative Site	Sittard-geleen		Netherlands	6162 BG
156	Novartis Investigative Site	Tilburg		Netherlands	5022 GC
157	Novartis Investigative Site	Oslo		Norway	0027
158	Novartis Investigative Site	Bialystok		Poland	15-276
159	Novartis Investigative Site	Chorzow		Poland	41-500
160	Novartis Investigative Site	Slupsk		Poland	76-200
161	Novartis Investigative Site	Szczecin		Poland	71-252
162	Novartis Investigative Site	Warszawa		Poland	02-097
163	Novartis Investigative Site	Warszawa		Poland	02-776
164	Novartis Investigative Site	Warszawa		Poland
165	Novartis Investigative Site	Wroclaw		Poland	50-367
166	Novartis Investigative Site	Wroclaw		Poland	53-439
167	Novartis Investigative Site	San Juan		Puerto Rico	00918
168	Novartis Investigative Site	Kazan		Russian Federation	420029
169	Novartis Investigative Site	Moscow		Russian Federation	115478
170	Novartis Investigative Site	Moscow		Russian Federation	125167
171	Novartis Investigative Site	Novosibirsk		Russian Federation	630087
172	Novartis Investigative Site	Penza		Russian Federation	440071
173	Novartis Investigative Site	St'Petersburg		Russian Federation	191024
174	Novartis Investigative Site	St'Petersburg		Russian Federation	197341
175	Novartis Investigative Site	St. Petersburg		Russian Federation	197 089
176	Novartis Investigative Site	Volgograd		Russian Federation	400138
177	Novartis Investigative Site	Hospitalet de Llobregat (Barcelona)		Spain	08907
178	Novartis Investigative Site	Madrid		Spain	28031
179	Novartis Investigative Site	Madrid		Spain	28040
180	Novartis Investigative Site	Salamanca		Spain	37007
181	Novartis Investigative Site	Sevilla		Spain	41013
182	Novartis Investigative Site	Toledo		Spain	45004
183	Novartis Investigative Site	Zaragoza		Spain	50009
184	Novartis Investigative Site	Goteborg		Sweden	SE-413 45
185	Novartis Investigative Site	Linkoping		Sweden	SE-581 85
186	Novartis Investigative Site	Lulea		Sweden	SE-971 80
187	Novartis Investigative Site	Orebro		Sweden	SE-701 85
188	Novartis Investigative Site	Stockholm		Sweden	SE 171 76
189	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
190	Novartis Investigative Site	Ankara		Turkey	06590
191	Novartis Investigative Site	Ankara		Turkey
192	Novartis Investigative Site	Istanbul		Turkey	34093
193	Novartis Investigative Site	Izmir		Turkey	35340
194	Novartis Investigative Site	Izmir		Turkey
195	Novartis Investigative Site	Cherkasy		Ukraine	18009
196	Novartis Investigative Site	Dnipropetrovsk		Ukraine	49102
197	Novartis Investigative Site	Kharkiv		Ukraine	61070
198	Novartis Investigative Site	Khmelnytskyi		Ukraine	29000
199	Novartis Investigative Site	Kyiv		Ukraine	03022
200	Novartis Investigative Site	Lviv		Ukraine	79044
201	Novartis Investigative Site	Makiivka		Ukraine	86132
202	Novartis Investigative Site	Vinnitsa		Ukraine	21018
203	Novartis Investigative Site	Zhytomyr		Ukraine	10002

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01039376

Other Study ID Numbers:

112517
COMB157C2301

First Posted:

Dec 25, 2009

Last Update Posted:

Jul 30, 2019

Last Verified:

Jul 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Novartis Pharmaceuticals

maintenance therapy

anti-CD20 monoclonal antibody

ofatumumab

Additional relevant MeSH terms:

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Ofatumumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Eligible participants were stratified based on complete or partial remission at study entry, number of previous induction treatments (2 versus 3) and type of prior treatment (chemoimmunotherapy, only alkylating monotherapy, or other treatment). Participants were then randomized in a 1:1 ratio to receive ofatumumab or no further treatment.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Period Title: Overall Study
STARTED	240	240
COMPLETED	110	114
NOT COMPLETED	130	126

Baseline Characteristics

Arm/Group Title	Ofatumumab	Observation	Total
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.	Total of all reporting groups
Overall Participants	240	240	480
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	121 50.4%	120 50%	241 50.2%
>=65 years	119 49.6%	120 50%	239 49.8%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.9 (10.31)	64.1 (9.61)	64.0 (9.96)
Sex: Female, Male (Count of Participants)
Female	79 32.9%	80 33.3%	159 33.1%
Male	161 67.1%	160 66.7%	321 66.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic/Latino	15 6.3%	18 7.5%	33 6.9%
Not Hispanic/Latino	225 93.8%	221 92.1%	446 92.9%
Missing	0 0%	1 0.4%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival, as Assessed by the Investigator
Description	Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the investigator according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [cm]), spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site); an increase by 50% or more in the previously noted enlargement of the liver or spleen; an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter; transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukemia.
Time Frame	From randomization until progression or death (up to 79 months)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized in the study.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
Median (95% Confidence Interval) [Months]	34.17	16.89

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Stratified log rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95% 0.43 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were obtained using the Pike estimator. A hazard ratio of <1 indicated a lower risk with ofatumumab maintenance compared with no further treatment.

2. Primary Outcome

Title	Progression-free Survival, as Assessed by the Independent Review Committee (IRC)
Description	Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the IRC according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [cm]), spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site); an increase by 50% or more in the previously noted enlargement of the liver or spleen; an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter; transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukemia.
Time Frame	From randomization until progression or death (up to 79 months)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized in the study.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
Median (95% Confidence Interval) [Months]	33.74	14.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Stratified log rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95% 0.42 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were obtained using the Pike estimator. A hazard ratio of <1 indicated a lower risk with ofatumumab maintenance compared with no further treatment.

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from randomization to date of death.
Time Frame	From randomization until death (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
Median (95% Confidence Interval) [Months]	NA	73.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6046
	Comments
	Method	Stratified log rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.69 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were obtained using the Pike estimator. A hazard ratio of <1 indicated a lower risk with ofatumumab maintenance compared with no further treatment.

4. Secondary Outcome

Title	Number of Participants With Improvement in Response From Baseline
Description	Improvement in response was assessed by calculating the percentage of participants who changed from partial response (PR) at Baseline to complete response during the study.
Time Frame	From Baseline until the end of the study (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population. Only participants who had PR at study entry were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	193	192
Number [Participants]	16 6.7%	8 3.3%

5. Secondary Outcome

Title	Time to Next Therapy
Description	Time to next therapy is defined as the time from randomization to the date of receiving the next CLL treatment.
Time Frame	From randomization until the end of the study (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
Median (95% Confidence Interval) [Months]	36.21	27.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0178
	Comments
	Method	Stratified log rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95% 0.62 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were obtained using the Pike estimator. A hazard ratio of <1 indicated a lower risk with ofatumumab maintenance compared with no further treatment.

6. Secondary Outcome

Title	Progression-free Survival After Next-line Therapy
Description	Progression-free survival after next-line therapy is defined as the time from randomization until progression or death following the next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy and who did not have progression or death after next-line therapy were censored at their last date of contact. Participant who died prior to next-line therapy, was counted as an event.
Time Frame	From randomization until progression or death (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population. Only participants who received next-line therapy and subjects who died prior to receiving next-line therapy were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	168	180
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3136
	Comments
	Method	log rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95% 0.42 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were obtained using the Pike estimator. A hazard ratio of <1 indicated a lower risk with ofatumumab maintenance compared with no further treatment.

7. Secondary Outcome

Title	Time to Progression After Next-line Therapy
Description	Time to progression after next-line therapy is defined as the time from progression following randomization until progression or death following next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy with a PD prior to receiving next line therapy and who did not had progression or death after next-line therapy were censored at their last date of contact. If a participant died prior to next-line therapy, this was counted as an event.
Time Frame	From randomization until progression or death (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population. Only participants who received next-line therapy and who also had PD prior to next line therapy were analysed. Participants who died prior to next-line therapy were also included for analysis.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	151	170
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1603
	Comments
	Method	log rank test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95% 0.29 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were obtained using the Pike estimator. A hazard ratio of <1 indicated a lower risk with ofatumumab maintenance compared with no further treatment.

8. Secondary Outcome

Title	Change From Baseline (BL) in the European Organization 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 Likert 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 = severe symptoms or problems. Changes from Baseline were analyzed by a mixed model-repeated measures analysis of covariance (ANCOVA).
Time Frame	From randomization until the end of the study (up to 47 months)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	238	236
Disease Effects Scale	0.36 (1.81)	2.56 (1.78)
Fatigue Scale	-0.16 (2.96)	3.63 (2.93)
Future Health Scale	-8.66 (3.69)	-5.08 (3.65)
Infection Scale	0.77 (2.20)	0.25 (2.17)
Social Problems Scale	5.69 (3.20)	10.02 (3.16)
Treatment Side Effects Scale	-0.54 (1.77)	1.95 (1.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0199
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.19
	Confidence Interval	(2-Sided) 95% -4.04 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Disease Effects Scale

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0085
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.79
	Confidence Interval	(2-Sided) 95% -6.61 to -0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	Fatigue Scale

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0642
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.58
	Confidence Interval	(2-Sided) 95% -7.37 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	Future Health Scale

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6398
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95% -1.67 to 2.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Infection Scale

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0055
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.32
	Confidence Interval	(2-Sided) 95% -7.37 to -1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Social Problems Scale

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0063
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.49
	Confidence Interval	(2-Sided) 95% -4.27 to -0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Side Effects Scale

9. Secondary Outcome

Title	Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
Description	The EORTC QLQ-C30 is a self-reported, 30-item cancer-specific instrument that assesses 15 domains: physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items), pain (2 items), fatigue (3 items), nausea and vomiting (2 items), five single-item symptom scores (insomnia, loss of appetite, constipation, diarrhea, and dyspnea), a single item asking about financial difficulties, and global health status/quality of life (QOF) consisting of 2 items. Functional and symptoms scales were measured on a four-point Likert scale, where 1 = not at all and 4 = very much, whereas global health status or QOF was assessed using a 7-item Likert scale, ranging from "poor" (worse quality of life) to "excellent" (better quality of life). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA.
Time Frame	From randomization until the end of the study (up to 47 months)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	238	236
Appetite Loss	-0.63 (2.33)	0.85 (2.30)
Cognitive Functioning	-1.63 (2.30)	-3.03 (2.29)
Constipation	-1.71 (2.30)	0.27 (2.27)
Diarrhoea	-1.99 (2.23)	-2.49 (2.20)
Dyspnoea	0.44 (2.71)	2.76 (2.67)
Emotional Functioning	-0.83 (2.47)	-4.72 (2.44)
Fatigue	-0.02 (2.89)	4.61 (2.85)
Financial Difficulties	4.09 (3.31)	5.85 (3.26)
Nausea and Vomiting	0.28 (1.12)	1.50 (1.11)
Pain	1.82 (2.89)	4.87 (2.87)
Physical Functioning	-2.25 (2.01)	-4.07 (2.01)
Global Health Status/QOL	-0.17 (2.52)	-1.94 (2.49)
Role Functioning	-6.94 (3.04)	-10.51 (3.00)
Social Functioning	-4.15 (2.71)	-7.80 (2.69)
Insomnia	-4.49 (3.51)	-2.70 (3.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1816
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95% -3.64 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Appetite Loss

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2863
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95% -1.18 to 3.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cognitive Functioning

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0932
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.97
	Confidence Interval	(2-Sided) 95% -4.28 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Constipation

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6533
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95% -1.67 to 2.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Diarrhoea

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0963
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.32
	Confidence Interval	(2-Sided) 95% -5.06 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dyspnoea

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0037
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.89
	Confidence Interval	(2-Sided) 95% 1.27 to 6.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Emotional Functioning

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0013
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.63
	Confidence Interval	(2-Sided) 95% -7.45 to -1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Fatigue

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2902
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.76
	Confidence Interval	(2-Sided) 95% -5.02 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Financial Difficulties

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0606
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.22
	Confidence Interval	(2-Sided) 95% -2.49 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Nausea and Vomiting

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0393
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.04
	Confidence Interval	(2-Sided) 95% -5.93 to -0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Pain

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0968
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 95% -0.33 to 3.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Physical Functioning

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1449
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.78
	Confidence Interval	(2-Sided) 95% -0.61 to 4.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Global Health Status/QOL

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0259
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.56
	Confidence Interval	(2-Sided) 95% 0.43 to 6.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Role Functioning

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0175
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.65
	Confidence Interval	(2-Sided) 95% 0.64 to 6.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Social Functioning

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3209
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.79
	Confidence Interval	(2-Sided) 95% -5.33 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	Insomnia

10. Secondary Outcome

Title	Change From Baseline in the Quality of Life Status as Assessed by the EuroQol-5D (EQ-5D) Scale
Description	EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (worst health) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA. A negative adjusted mean change from Baseline represents a worsening of quality of life.
Time Frame	From screening until the end of the study (up to 47 months)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	238	236
Utility Score	-0.02 (0.03)	-0.05 (0.03)
Thermometer Score	-0.37 (2.05)	-1.75 (2.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0110
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95% 0.01 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Utility Score

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Observation
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1999
	Comments	The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
	Method	Repeated measures analysis of covariance
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95% -0.73 to 3.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Thermometer Score

11. Secondary Outcome

Title	Number of Participants With an Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the Indicated Time Points
Description	Improvement is defined as a decrease from Baseline by at least one step on the ECOG performance status scale (improvement categorized as yes or no). Improvement in ECOG performance status was measured.
Time Frame	From randomization until the end of the study (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
C1 W2/M1	10 4.2%	12 5%
C2 W9/M3	20 8.3%	17 7.1%
C3 W17/M5	16 6.7%	17 7.1%
C4 W25/M7	18 7.5%	16 6.7%
C5 W33/M9	16 6.7%	18 7.5%
C6 W41/M11	14 5.8%	12 5%
C7 W49/M13	18 7.5%	14 5.8%
C8 W57/M15	14 5.8%	15 6.3%
C9 W65/M17	11 4.6%	12 5%
C10 W73/M19	14 5.8%	10 4.2%
C11 W81/M21	10 4.2%	9 3.8%
C12 W89/M23	11 4.6%	7 2.9%
C13 W97/M25	9 3.8%	7 2.9%
3M FU	11 4.6%	6 2.5%
6M FU	9 3.8%	4 1.7%
9M FU	5 2.1%	5 2.1%
12M FU	6 2.5%	5 2.1%
15M FU	4 1.7%	4 1.7%
18M FU	4 1.7%	3 1.3%
21M FU	3 1.3%	3 1.3%
24M FU	3 1.3%	2 0.8%
27M FU	3 1.3%	1 0.4%
30M FU	3 1.3%	1 0.4%
33M FU	3 1.3%	1 0.4%
36M FU	3 1.3%	1 0.4%
39M FU	1 0.4%	2 0.8%
42M FU	0 0%	0 0%
45M FU	0 0%	1 0.4%
48M FU	0 0%	1 0.4%
51M FU	0 0%	1 0.4%
54M FU	1 0.4%	1 0.4%
57M FU	0 0%	1 0.4%
60M FU	0 0%	1 0.4%
Withdrawal	5 2.1%	10 4.2%
Worst-Case Post Baseline	3 1.3%	5 2.1%

12. Secondary Outcome

Title	Number of Participants With the Indicated Constitutional or B-symptoms at the Indicated Time Points
Description	Participants with the indicated constitutional or B-symptoms (night sweats [without signs of infection]; unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of > 38 degrees celcius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue) were presented. The proportion of participants with no night sweats, no weight loss, no fever and no extreme fatigue were summarized.
Time Frame	From Screening until the end of the study (up to 88 months)

Outcome Measure Data

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

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
SCR, extreme fatigue	0 0%	7 2.9%
SCR, fever	0 0%	1 0.4%
SCR, night sweats	13 5.4%	8 3.3%
SCR, weight loss	2 0.8%	1 0.4%
C1 W2/M1, extreme fatigue	0 0%	2 0.8%
C1 W2/M1, fever	0 0%	0 0%
C1 W2/M1, night sweats	9 3.8%	6 2.5%
C1 W2/M1, weight loss	4 1.7%	1 0.4%
C2 W9/M3, extreme fatigue	3 1.3%	3 1.3%
C2 W9/M3, fever	1 0.4%	2 0.8%
C2 W9/M3, night sweats	6 2.5%	10 4.2%
C2 W9/M3, weight loss	3 1.3%	1 0.4%
C3 W17/M5, extreme fatigue	4 1.7%	5 2.1%
C3 W17/M5, fever	1 0.4%	2 0.8%
C3 W17/M5, night sweats	6 2.5%	10 4.2%
C3 W17/M5, weight loss	3 1.3%	3 1.3%
C4 W25/M7, extreme fatigue (n=203, 187)	1 0.4%	3 1.3%
C4 W25/M7, fever	1 0.4%	2 0.8%
C4 W25/M7, night sweats	5 2.1%	7 2.9%
C4 W25/M7, weight loss	1 0.4%	1 0.4%
C5 W33/M9, extreme fatigue	1 0.4%	5 2.1%
C5 W33/M9, fever	1 0.4%	0 0%
C5 W33/M9, night sweats fatigue	7 2.9%	8 3.3%
C5 W33/M9, weight loss	0 0%	4 1.7%
C6 W41/M11, extreme fatigue	1 0.4%	2 0.8%
C6 W41/M11, fever	2 0.8%	0 0%
C6 W41/M11, night sweats	7 2.9%	7 2.9%
C6 W41/M11, weight loss	0 0%	0 0%
C7 W49/M13, extreme fatigue	1 0.4%	1 0.4%
C7 W49/M13, fever	0 0%	0 0%
C7 W49/M13, night sweats	3 1.3%	5 2.1%
C7 W49/M13, weight loss	2 0.8%	1 0.4%
C8 W57/M15, extreme fatigue	1 0.4%	1 0.4%
C8 W57/M15, fever	2 0.8%	0 0%
C8 W57/M15, night sweats	4 1.7%	4 1.7%
C8 W57/M15, weight loss	2 0.8%	3 1.3%
C9 W65/M17, extreme fatigue	2 0.8%	2 0.8%
C9 W65/M17, fever	2 0.8%	0 0%
C9 W65/M17, night sweats	7 2.9%	4 1.7%
C9 W65/M17, weight loss	1 0.4%	2 0.8%
C10 W73/M19, extreme fatigue	2 0.8%	2 0.8%
C10 W73/M19, fever	1 0.4%	0 0%
C10 W73/M19, night sweats	7 2.9%	4 1.7%
C10 W73/M19, weight loss	2 0.8%	1 0.4%
C11 W81/M21, extreme fatigue	0 0%	3 1.3%
C11 W81/M21, fever	1 0.4%	0 0%
C11 W81/M21, night sweats	2 0.8%	4 1.7%
C11 W81/M21, weight loss	0 0%	0 0%
C12 W89/M23, extreme fatigue	1 0.4%	0 0%
C12 W89/M23, fever	0 0%	0 0%
C12 W89/M23, night sweats	3 1.3%	3 1.3%
C12 W89/M23, weight loss	0 0%	1 0.4%
C13 W97/M25, extreme fatigue	1 0.4%	0 0%
C13 W97/M25, fever	0 0%	0 0%
C13 W97/M25, night sweats	2 0.8%	1 0.4%
C13 W97/M25, weight loss	1 0.4%	3 1.3%
3M follow up, extreme fatigue	3 1.3%	2 0.8%
3M follow up, fever	1 0.4%	1 0.4%
3M follow up, night sweats	4 1.7%	4 1.7%
3M follow up, weight loss	2 0.8%	0 0%
6M follow up, extreme fatigue	3 1.3%	2 0.8%
6M follow up, fever	1 0.4%	0 0%
6M follow up, night sweats	2 0.8%	2 0.8%
6M follow up, weight loss	1 0.4%	1 0.4%
9M follow up, extreme fatigue	2 0.8%	2 0.8%
9M follow up, fever	0 0%	0 0%
9M follow up, night sweats	4 1.7%	2 0.8%
9M follow up, weight loss	0 0%	2 0.8%
12M follow up, extreme fatigue	0 0%	3 1.3%
12M follow up, fever	1 0.4%	1 0.4%
12M follow up, night sweats	2 0.8%	4 1.7%
12M follow up, weight loss	0 0%	1 0.4%
15M follow up, extreme fatigue	0 0%	0 0%
15M follow up, fever	0 0%	1 0.4%
15M follow up, night sweats	2 0.8%	1 0.4%
15M follow up, weight loss	1 0.4%	0 0%
18M follow up, extreme fatigue	1 0.4%	1 0.4%
18M follow up, fever	0 0%	0 0%
18M follow up, night sweats	2 0.8%	1 0.4%
18M follow up, weight loss	0 0%	0 0%
21M follow up, extreme fatigue	0 0%	1 0.4%
21M follow up, fever	0 0%	0 0%
21M follow up, night sweats	1 0.4%	2 0.8%
21M follow up, weight loss	0 0%	0 0%
27M follow up, extreme fatigue	0 0%	0 0%
27M follow up, fever	0 0%	0 0%
27M follow up, night sweats	2 0.8%	1 0.4%
27M follow up, weight loss	1 0.4%	1 0.4%
30M follow up, extreme fatigue	0 0%	0 0%
30M follow up, fever	0 0%	0 0%
30M follow up, night sweats	1 0.4%	1 0.4%
30M follow up, weight loss	0 0%	0 0%
33M follow up, extreme fatigue	0 0%	0 0%
33M follow up, fever	1 0.4%	0 0%
33M follow up, night sweats	2 0.8%	2 0.8%
33M follow up, weight loss	0 0%	0 0%
36M follow up, extreme fatigue	1 0.4%	0 0%
36M follow up, fever	0 0%	0 0%
36M follow up, night sweats	1 0.4%	0 0%
36M follow up, weight loss	0 0%	0 0%
39M follow up, extreme fatigue	1 0.4%	0 0%
39M follow up, fever	0 0%	0 0%
39M follow up, night sweats	1 0.4%	0 0%
39M follow up, weight loss	0 0%	0 0%
42M follow up, extreme fatigue	0 0%	0 0%
42M follow up, fever	0 0%	1 0.4%
42M follow up, night sweats	0 0%	1 0.4%
42M follow up,, weight loss	0 0%	0 0%
51M follow up, extreme fatigue	0 0%	0 0%
51M follow up, fever	1 0.4%	0 0%
51M follow up, night sweats	0 0%	1 0.4%
51M follow up, weight loss	0 0%	0 0%
54M follow up, extreme fatigue	0 0%	0 0%
54M follow up, fever	1 0.4%	0 0%
54M follow up, night sweats	0 0%	0 0%
54M follow up, weight loss	0 0%	0 0%
Withdrawal, extreme fatigue	9 3.8%	12 5%
Withdrawal, fever	7 2.9%	3 1.3%
Withdrawal, night sweats	14 5.8%	15 6.3%
Withdrawal, weight loss	4 1.7%	10 4.2%

13. Secondary Outcome

Title	Number of Participants With Grade 3 and Above Adverse Event of Infection
Description	Participants with Grade 3, Grade 4 and Grade 5 adverse event of infection are presented. Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.0 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death).
Time Frame	From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 26 months)

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who were randomized in the study and analyses were done based on the treatment the participant received regardless of how they were randomized.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	241
Number [Participants]	38 15.8%	23 9.6%

14. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	241
Any AE	221 92.1%	198 82.5%
Any SAE	120 50%	120 50%

15. Secondary Outcome

Title	Number of Participants With a Grade 3 or Grade 4 Myelosuppression (Anemia, Neutropenia, or Thrombocytopenia) at Indicated Time Points
Description	Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Number of participants who reported myelosuppression (anemia [low hemoglobin count], neutropenia [low neutrophil count], and thrombocytopenia [low platelet count]) are presented. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 4.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).
Time Frame	From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until the end of the study for SAEs (88 months)

Outcome Measure Data

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

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	241
SCR	7 2.9%	5 2.1%
C1 W1/M1	1 0.4%	1 0.4%
C1 W2/M1	13 5.4%	8 3.3%
C2 W9/M3	12 5%	15 6.3%
C2, unscheduled	1 0.4%	0 0%
C3 W17/M5	18 7.5%	7 2.9%
C3, unscheduled	1 0.4%	0 0%
C4 W25/M7	12 5%	8 3.3%
C4 Unscheduled	1 0.4%
C5 W33/M9	15 6.3%	5 2.1%
C5, unscheduled	1 0.4%
C6 W41/M11	13 5.4%	5 2.1%
C6 unscheduled_1	4 1.7%
C6 unscheduled_2	1 0.4%
C7 W49/M13	9 3.8%	2 0.8%
C8 W57/M15	10 4.2%	3 1.3%
C9 W65/M17	5 2.1%	1 0.4%
C9, unscheduled	0 0%	1 0.4%
C10 W73/M19	2 0.8%	2 0.8%
C11 W81/M21	5 2.1%	1 0.4%
C11 unscheduled_1	1 0.4%	0 0%
C11 unscheduled_2	1 0.4%
C12 W89/M23	3 1.3%	2 0.8%
C13 W97/M25	3 1.3%	2 0.8%
C13, unscheduled	1 0.4%
3M follow-up	2 0.8%	1 0.4%
6M follow-up	2 0.8%	1 0.4%
9M follow-up	2 0.8%	1 0.4%
12M follow-up	1 0.4%	2 0.8%
15M follow-up	1 0.4%	0 0%
18M follow-up	0 0%	1 0.4%
27M follow-up	0 0%	1 0.4%
30M follow-up	0 0%	1 0.4%
33M follow-up	1 0.4%	0 0%
60M follow-up	1 0.4%	0 0%
Withdrawal	11 4.6%	8 3.3%
Unscheduled_1	0 0%	1 0.4%
Unscheduled_2	0 0%	2 0.8%
Unscheduled_3	1 0.4%	0 0%

16. Secondary Outcome

Title	Number of Participants Who Received at Least One Transfusion During the Study
Description	Participants who received at least one transfusion (any blood products or blood supportive care product) during the study are presented.
Time Frame	From randomization until the end of the study (up to 88 months)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	241
Number [Participants]	96 40%	64 26.7%

17. Secondary Outcome

Title	Number of Participants Diagnosed With Autoimmune Hemolytic Anemia (AIHA)
Description	AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.
Time Frame	From randomization until the end of the study (up to 88 months)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	241
Haemolytic anaemia	2 0.8%	2 0.8%
Autoimmune haemolytic anaemia	1 0.4%	4 1.7%
Thrombocytopenic purpura	0 0%	1 0.4%

18. Secondary Outcome

Title	Number of Participants With a Positive Anti-ofatumumab Antibody (Human Anti-human Antibody; HAHA) Result
Description	All serum samples for analysis of HAHA were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA positive and further evaluated in the titration test to obtain a titer of HAHA. A confirmed positive result at any time point means the participant is positive for HAHA.Results are reported as the number of participants positive for HAHA.
Time Frame	Pre-dose (Visit 1), Months 7, 13, 19, and 25 during treatment and at 3 and 6 months after last ofatumumab dose (up to 30 months)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with post-ofatumumab HAHA results were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	0
Number [Participants]	1 0.4%

19. Secondary Outcome

Title	Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM at Indicated Time Points
Description	Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-baseline value minus the Baseline value.
Time Frame	Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 88 months)

Outcome Measure Data

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

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	239	241
IgA, C2 W9, M3	0.2 (0.23)
IgA, C3 W17, M5	0.0 (0.12)	-0.1 (0.24)
IgA, C4 W25, M7	-0.1 (0.17)	-0.0 (0.41)
IgA, C5 W33, M9	-0.0 (NA)	-0.0 (0.01)
IgA, C6 W41, M11	0.0 (NA)	-0.1 (NA)
IgA, C7 W49, M13	-0.1 (0.24)	-0.0 (0.63)
IgA, C8 W57, M15	-0.1 (0.15)	0.0 (0.02)
IgA, C9 W65, M17	-0.2 (0.17)	0.1 (0.04)
IgA, C10 W73, M19	-0.1 (0.20)	0.1 (0.37)
IgA, C11 W81, M21	-0.0 (NA)	0.2 (0.21)
IgA, C12 W89, M23	-0.3 (NA)	0.2 (0.39)
IgA, C13 W97, M25	-0.1 (0.23)	0.1 (0.38)
IgA, 3M FU	-0.1 (0.22)	0.2 (0.37)
IgA, 6M FU	-0.1 (0.18)	0.1 (0.39)
IgA, 9M FU	-0.1 (0.22)	0.1 (0.38)
IgA, 12M FU	-0.1 (0.30)	0.2 (0.36)
IgA, 15M FU	-0.0 (0.27)	0.2 (0.44)
IgA, 18M FU	0.1 (0.57)	0.1 (0.25)
IgA, 21M FU	-0.1 (0.40)	0.1 (0.34)
IgA, 24M FU	0.2 (1.06)	0.1 (0.37)
IgA, 27M FU	0.1 (0.70)	0.1 (0.46)
IgA, 30M FU	0.2 (0.85)	0.1 (0.58)
IgA, 33M FU	0.4 (1.48)	0.2 (0.60)
IgA, 36M FU	0.2 (1.06)	0.2 (0.63)
IgA, 39M FU	0.2 (0.86)	0.3 (0.71)
IgA, 42M FU	0.4 (1.67)	0.2 (0.72)
IgA, 45M FU	-0.2 (0.20)	0.4 (0.94)
IgA, 48M FU	-0.1 (0.83)	-0.0 (0.25)
IgA, 51M FU	0.3 (1.15)	0.2 (0.70)
IgA, 54M FU	0.0 (0.89)	0.7 (1.34)
IgA, 57M FU	-0.4 (0.36)	0.4 (1.04)
IgA, 60M FU	-0.5 (0.42)	0.4 (1.05)
IgA, Withdrawal	0.0 (0.53)	-0.1 (0.08)
IgG, C2 W9, M3	-0.4 (0.21)
IgG, C3 W17, M5	0.0 (1.17)	0.2 (0.39)
IgG, C4 W25, M7	-0.7 (2.03)	-0.1 (1.83)
IgG, C5 W33, M9	-1.0 (NA)	0.5 (2.20)
IgG, C6 W41, M11	-1.9 (NA)	1.0 (NA)
IgG, C7 W49, M13	-1.1 (1.9)	0.2 (2.88)
IgG, C8 W57, M15	-1.3 (1.03)	-0.9 (0.08)
IgG, C9 W65, M17	-3.7 (4.96)	0.9 (0.71)
IgG, C10 W73, M19	-1.0 (2.15)	0.6 (4.61)
IgG, C11 W81, M21	0.2 (NA)	-0.3 (1.39)
IgG, C12 W89, M23	-0.5 (NA)	0.2 (0.89)
IgG, C13 W97, M25	-1.1 (2.45)	0.3 (3.02)
IgG, 3M FU	-0.7 (2.46)	0.2 (2.83)
IgG, 6M FU	-0.9 (2.24)	0.2 (2.89)
IgG, 9M FU	-0.7 (2.29)	0.1 (2.87)
IgG, 12M FU	-0.5 (2.17)	-0.3 (3.26)
IgG, 15M FU	-0.4 (2.49)	-0.1 (3.29)
IgG, 18M FU	-0.5 (2.71)	-0.3 (3.45)
IgG, 21M FU	-0.9 (2.39)	0.1 (3.81)
IgG, 24M FU (	-0.1 (2.17)	0.0 (3.43)
IgG, 27M FU	-0.3 (2.32)	-0.5 (3.97)
IgG, 30M FU	0.3 (2.67)	-0.9 (4.83)
IgG, 33M FU	0.7 (2.91)	-1.1 (5.63)
IgG, 36M FU	-0.1 (2.71)	-1.2 (3.87)
IgG, 39M FU	0.3 (2.53)	-0.9 (5.60)
IgG, 42M FU	0.6 (3.03)	0.9 (4.82)
IgG, 45M FU	-0.6 (2.11)	2.3 (4.00)
IgG, 48M FU	-0.6 (2.30)	3.5 (3.14)
IgG, 51M FU	0.1 (3.25)	2.4 (4.02)
IgG, 54M FU	-1.0 (2.35)	5.6 (4.14)
IgG, 57M FU	1.3 (4.01)	5.3 (5.68)
IgG, 60M FU	0.8 (4.43)	4.6 (4.28)
IgG, Withdrawal	-0.7 (0.91)	-1.5 (1.86)
IgM, C2 W9, M3	0.1 (0.12)
IgM, C3 W17, M5	-0.0 (0.09)	-0.0 (0.06)
IgM, C4 W25, M7	-0.1 (0.43)	0.1 (0.42)
IgM, C5 W33, M9	-0.1 (NA)	-0.1 (0.07)
IgM, C6 W41, M11	-0.5 (NA)	0.0 (NA)
IgM, C7 W49, M13	-0.1 (0.29)	0.2 (0.90)
IgM, C8 W57, M15	-0.0 (0.05)	-0.0 (0.01)
IgM, C9 W65, M17	-0.3 (0.54)	0.3 (0.49)
IgM, C10 W73, M19	-0.1 (0.36)	0.2 (0.86)
IgM, C11 W81, M21	0.0 (NA)	0.2 (0.04)
IgM, C12 W89, M23	0.0 (NA)	-0.0 (0.11)
IgM, C13 W97, M25	-0.1 (0.45)	0.2 (0.79)
IgM, 3M FU	-0.0 (0.35)	0.3 (1.30)
IgM, 6M FU (	-0.1 (0.36)	0.4 (1.60)
IgM, 9M FU	-0.1 (0.17)	0.6 (2.93)
IgM, 12M FU	-0.0 (0.18)	0.6 (2.49)
IgM, 15M FU	-0.0 (0.15)	0.3 (1.08)
IgM, 18M FU	0.1 (0.25)	1.2 (4.95)
IgM, 21M FU	0.1 (0.41)	1.4 (5.48)
IgM, 24M FU	0.0 (0.14)	2.0 (8.19)
IgM, 27M FU	0.2 (0.41)	-0.2 (1.14)
IgM, 30M FU (n=18, 12)	0.1 (0.17)	-0.0 (1.51)
IgM, 33M FU	0.1 (0.22)	0.1 (0.36)
IgM, 36M FU	0.2 (0.28)	-0.3 (1.31)
IgM, 39M FU	0.1 (0.21)	-0.4 (1.54)
IgM, 42M FU	0.1 (0.23)	-0.6 (1.79)
IgM, 45M FU	0.2 (0.32)	0.2 (0.27)
IgM, 48M FU	0.1 (0.28)	0.4 (0.38)
IgM, 51M FU	-0.0 (0.06)	0.3 (0.39)
IgM, 54M FU	0.1 (0.24)	0.5 (0.26)
IgM, 57M FU	0.2 (0.49)	0.4 (0.41)
IgM, 60M FU	0.6 (0.84)	0.4 (0.42)
IgM, Withdrawal	0.3 (0.73)	-0.0 (0.03)

20. Secondary Outcome

Title	Number of Participants Who Were Positive and Negative for Minimal Residual Disease (MRD) at Any Visit
Description	MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed complete remission. Number of participants who were positive and negative for minimal residual disease (MRD) at any visit is presented.
Time Frame	From randomization until the end of the study (up to 88 months)

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with data available at the specified time point were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
Positive	150 62.5%	122 50.8%
Negative	27 11.3%	37 15.4%

21. Secondary Outcome

Title	Change From Baseline in Cluster of Differentiation (CD) CD5+CD19+ and CD5-CD19+ Cell Counts at the Indicated Time Points
Description	CD5+CD19+ cells were counted by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline CD5+CD19+ and CD5-CD19+ cell count value is the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline and every two months from Month 3 until Month 25 and at every followup (up to 88 months)

Outcome Measure Data

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

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
CD5+CD19+, C2 W9, M3	-284.1 (2101.26)	598.6 (3155.69)
CD5+CD19+, C3 W17, M5	52.0 (3554.94)	750.5 (1995.47)
CD5+CD19+, C4 W25, M7	-177.6 (4105.41)	2102.2 (9866.31)
CD5+CD19+, C5 W33, M9	-113.6 (3336.44)	1905.2 (6104.84)
CD5+CD19+, C6 W41, M11	-450.3 (2851.41)	1550.9 (5483.76)
CD5+CD19+, C7 W49, M13	-505.3 (2716.66)	1429.2 (4408.69)
CD5+CD19+, C8 W57, M15	-625.9 (3003.35)	1107.6 (3371.04)
CD5+CD19+, C9 W65, M17	-649.5 (3057.32)	967.0 (1826.90)
CD5+CD19+, C10 W73, M19	-238.6 (4061.13)	1146.0 (1914.02)
CD5+CD19+, C11 W81, M21	-579.0 (3446.95)	1656.7 (2662.28)
CD5+CD19+, C12 W89, M23	-569.5 (3510.43)	1608.3 (3220.20)
CD5+CD19+, C13 W97, M25	-361.3 (2702.79)	2059.0 (4987.97)
CD5+CD19+, 3M FU	121.1 (5479.03)	2143.9 (4280.66)
CD5+CD19+, 6M FU	1968.3 (15975.52)	2363.5 (4937.00)
CD5+CD19+, 9M FU	1411.3 (6965.41)	4008.5 (13550.03)
CD5+CD19+, 12M FU	2198.5 (10743.58)	2316.0 (8763.12)
CD5+CD19+, 15M FU	-84.4 (4140.77)	1246.2 (2894.20)
CD5+CD19+, 18M FU	1844.1 (10091.28)	1250.9 (3182.14)
CD5+CD19+, 21M FU	-395.1 (4521.30)	1147.5 (2191.69)
CD5+CD19+, 24M FU	279.4 (6250.23)	2354.0 (6726.31)
CD5+CD19+, 27M FU	-368.6 (4829.16)	2250.8 (5833.72)
CD5+CD19+, 30M FU	-354.4 (5686.14)	2189.3 (6246.05)
CD5+CD19+, 33M FU	-397.0 (2767.27)	3024.8 (7543.26)
CD5+CD19+, 36M FU	-354.8 (2767.77)	3668.4 (8581.98)
CD5+CD19+, 39M FU	-163.7 (3116.92)	1217.1 (2441.59)
CD5+CD19+, 42M FU	-81.7 (3426.53)	2005.9 (4327.53)
CD5+CD19+, 45M FU	466.9 (919.60)	450.4 (1031.86)
CD5+CD19+, 48M FU	1255.3 (2289.34)	643.4 (1270.16)
CD5+CD19+, 51M FU	4341.4 (8803.05)	1104.8 (2004.49)
CD5+CD19+, 54M FU	1689.8 (2357.27)	237.5 (251.02)
CD5+CD19+, 57M FU	703.3 (898.82)	186.0 (145.66)
CD5+CD19+, 60M FU	237.0 (326.68)	278.5 (392.44)
CD5+CD19+, withdrawal	8916.4 (25922.35)	13991.9 (23553.42)
CD5-CD19+, C2 W9, M3	-17.9 (588.42)	81.1 (781.76)
CD5-CD19+, C3 W17, M5	5.2 (358.12)	50.7 (168.87)
CD5-CD19+, C4 W25, M7	73.9 (687.62)	228.2 (2037.16)
CD5-CD19+, C5 W33, M9	87.5 (971.22)	98.9 (401.27)
CD5-CD19+, C6 W41, M11	-13.1 (257.81)	92.7 (296.23)
CD5-CD19+, C7 W49, M13	5.3 (368.66)	77.5 (125.81)
CD5-CD19+, C8 W57, M15	-13.3 (279.89)	95.9 (143.95)
CD5-CD19+, C9 W65, M17	-4.4 (349.91)	128.3 (294.11)
CD5-CD19+, C10 W73, M19	3.3 (421.97)	172.5 (555.27)
CD5-CD19+, C11 W81, M21	-20.7 (303.21)	127.2 (150.18)
CD5-CD19+, C12 W89, M23	-13.5 (306.57)	143.7 (251.88)
CD5-CD19+, C13 W97, M25	7.9 (103.85)	184.0 (403.97)
CD5-CD19+, 3M FU	27.4 (522.67)	145.7 (229.93)
CD5-CD19+, 6M FU	22.6 (428.70)	153.8 (330.63)
CD5-CD19+, 9M FU	13.2 (368.63)	140.9 (107.92)
CD5-CD19+, 12M FU	86.4 (769.73)	147.2 (136.93)
CD5-CD19+, 15M FU	10.8 (393.47)	154.8 (120.86)
CD5-CD19+, 18M FU	84.7 (146.38)	173.5 (142.95)
CD5-CD19+, 21M FU	16.2 (450.95)	175.9 (158.31)
CD5-CD19+, 24M FU	574.7 (2993.58)	223.2 (200.06)
CD5-CD19+, 27M FU	102.0 (643.44)	153.3 (110.37)
CD5-CD19+, 30M FU	38.7 (271.84)	142.9 (106.57)
CD5-CD19+, 33M FU	98.3 (117.18)	157.5 (96.69)
CD5-CD19+, 36M FU	141.1 (179.33)	215.2 (298.90)
CD5-CD19+, 39M FU	134.3 (167.33)	183.9 (249.78)
CD5-CD19+, 42M FU	113.3 (131.48)	361.1 (601.36)
CD5-CD19+, 45M FU	108.6 (140.97)	157.7 (116.04)
CD5-CD19+, 48M FU	147.7 (185.10)	180.6 (175.93)
CD5-CD19+, 51M FU	162.6 (229.87)	139.3 (82.75)
CD5-CD19+, 54M FU	221.2 (217.75)	315.0 (43.84)
CD5-CD19+, 57M FU	138.3 (196.32)	195.5 (17.68)
CD5-CD19+, 60M FU	180.5 (222.74)	127.0 (173.95)
CD5-CD19+, withdrawal	593.5 (2028.89)	552.7 (1799.49)

22. Secondary Outcome

Title	Summary of Covariates to Compute Cox Proportional Hazards Regression Model for Relationship Between Investigator Assessed Progression-free Survival and the Indicated Prognostic Markers
Description	Blood samples were collected for the assessment of the following prognostic markers at Baseline (BL) and upon relapse: immunoglobulin heavy chain variable region (IgVH) mutational status; VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]) including 6q-, 11q-, +12q, 17p-, 13q- deletions; beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH) at BL, IgVH mutational status at BL, beta 2 microglobulin at BL, BL CD20 and BL complement level. For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=CY G.
Time Frame	From Baseline until the end of the study (up to 79 months)

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	240	240
CY G: 6q- or +12q or 13q	36 15%	12 5%
CY G: 17p-	7 2.9%	4 1.7%
CY G: 11q-	11 4.6%	10 4.2%
CY G: no aberration	166 69.2%	181 75.4%
CY G: missing	20 8.3%	33 13.8%
B2 Microglobulin G 2: > 3500 μg/L	80 33.3%	68 28.3%
B2 Microglobulin G 2: <=3500 μg/L	157 65.4%	171 71.3%
B2 Microglobulin G 2: missing	3 1.3%	1 0.4%
IgVH Mutational Status 1: mutated	54 22.5%	74 30.8%
IgVH Mutational Status 1: unmutated	139 57.9%	116 48.3%
IgVH Mutational Status 1: not available	3 1.3%	1 0.4%
IgVH Mutational Status 1: missing	44 18.3%	49 20.4%
VH3-21 Usage Flag: Yes	7 2.9%	7 2.9%
VH3-21 Usage Flag: No	233 97.1%	233 97.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.547
	Confidence Interval	(2-Sided) 95% 1.051 to 2.276
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated for Cytogenetics Group (based on >=20% cut-off) with 6q-, or +12q or 13q-/no abberation

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	9.303
	Confidence Interval	(2-Sided) 95% 4.934 to 17.540
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated for Cytogenetics Group (based on >=20% cut-off) with 17p-/no abberation

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	4.219
	Confidence Interval	(2-Sided) 95% 2.468 to 7.210
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated for Cytogenetics Group (based on >=20% cut-off) with 11q-/no abberation

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.832
	Confidence Interval	(2-Sided) 95% 1.434 to 2.339
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated for B2 Microglobulin Group 2 with 3500 as cut off: >3500 ug/L/<=3500 ug/L

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.573
	Confidence Interval	(2-Sided) 95% 0.432 to 0.760
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated for IgVH Mutational Status 1 Mutated/Unmutated

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.301
	Confidence Interval	(2-Sided) 95% 0.692 to 2.448
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR estimated for VH3-21 Usage Flag Yes/No.

23. Secondary Outcome

Title	Cmax and Ctrough of Ofatumumab
Description	Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected at pre-dose and 0.5 hours after the end of the infusion at treatment on Month 1 Week 1 (Day 1), Month 1 Week 2 (Day 8), and at every second infusion.
Time Frame	Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Population: all participants in the ITT Population for whom a PK sample was obtained and analyzed. Only those participants available at the indicated time points (indicated by n=X in the category titles) were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	221	0
Cmax, Cycle 1 Week 1	73.8 (65)
Cmax, Cycle 1 Week 2	264 (50)
Cmax, Cycle 4	275 (31)
Ctrough, Cycle 1 Week 2	16.3 (254)
Ctrough, Cycle 4	9.9 (1323)

24. Secondary Outcome

Title	Total Plasma Clearance (CL) of Ofatumumab
Description	Plasma clearance is defined as the plasma volume that is cleared of drug per unit of time.
Time Frame	Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants available at the indicated time points (indicated by n=X in the category titles) were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	190	0
Cycle 1 Week 1	49.1 (38)
Cycle 1 Week 2	9.6 (43)
Cycle 4	8.1 (50)

25. Secondary Outcome

Title	AUC(0-tau) of Ofatumumab
Description	Area under the concentration time curve over the dosing interval (AUC[0-tau]) is a measure of the drug exposure over time.
Time Frame	Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants available at the indicated time points (indicated by n=X in the category titles) were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	190	0
Cycle 1 Week 1	6113 (38)
Cycle 1 Week 2	104013 (43)
Cycle 4	122782 (50)

26. Secondary Outcome

Title	Vss of Ofatumumab
Description	Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of a drug between plasma and the rest of the body at steady state. Data from all time points collected were used to calculate one Vss value for each individual.
Time Frame	Day 1 Month 1 ( Cycle 1) through Month 7 ( Cycle 4)

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	224	0
Geometric Mean (Geometric Coefficient of Variation) [Liters (L)]	6.0 (27)

27. Secondary Outcome

Title	Plasma Half-life (t1/2) of Ofatumumab
Description	The terminal half life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original value.
Time Frame	Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants available at the indicated time points (indicated by n=X in the category titles) were analyzed.

Arm/Group Title	Ofatumumab	Observation
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.	Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
Measure Participants	190	0
Cycle 1 Week 1	126 (35)
Cycle 1 Week 2	458 (36)
Cycle 4	542 (48)

Adverse Events

	Ofatumumab		Observation		Total
Time Frame	From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months).
Adverse Event Reporting Description	All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 88 months.

Arm/Group Title	Ofatumumab		Observation		Total
Arm/Group Description	Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.		Participants with relapsed CLL received no treatment and were under observation for up to 2 years.		All patients
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/239 (36.8%)		87/241 (36.1%)		175/480 (36.5%)
Serious Adverse Events
	Ofatumumab		Observation		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	120/239 (50.2%)		120/241 (49.8%)		240/480 (50%)
Blood and lymphatic system disorders
Agranulocytosis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Anaemia	5/239 (2.1%)		7/241 (2.9%)		12/480 (2.5%)
Autoimmune haemolytic anaemia	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Febrile neutropenia	18/239 (7.5%)		10/241 (4.1%)		28/480 (5.8%)
Haemolytic anaemia	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Immune thrombocytopenic purpura	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Leukopenia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Lymphadenopathy	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Neutropenia	5/239 (2.1%)		5/241 (2.1%)		10/480 (2.1%)
Pancytopenia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Splenic infarction	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Thrombocytopenia	1/239 (0.4%)		3/241 (1.2%)		4/480 (0.8%)
Thrombocytopenic purpura	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Cardiac disorders
Acute coronary syndrome	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Angina pectoris	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Angina unstable	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Aortic valve stenosis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Atrial fibrillation	2/239 (0.8%)		2/241 (0.8%)		4/480 (0.8%)
Atrial flutter	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Bradycardia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cardiac arrest	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Cardiac failure	3/239 (1.3%)		2/241 (0.8%)		5/480 (1%)
Cardiac failure acute	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Cardiogenic shock	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Cardiomyopathy	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Myocardial infarction	1/239 (0.4%)		3/241 (1.2%)		4/480 (0.8%)
Myocardial ischaemia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Stress cardiomyopathy	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Ventricular fibrillation	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Ear and labyrinth disorders
Deafness	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Vertigo	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Vertigo positional	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Eye disorders
Diplopia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Gastrointestinal disorders
Abdominal pain	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Abdominal pain upper	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Colitis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Diarrhoea	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Dysphagia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Enterocolitis	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Eosinophilic colitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Gastrointestinal haemorrhage	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Ileus	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Inguinal hernia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Intestinal infarction	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Intestinal obstruction	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Large intestine polyp	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Lower gastrointestinal haemorrhage	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Nausea	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Oesophageal spasm	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Oesophagitis	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Pancreatitis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Rectal haemorrhage	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Small intestinal obstruction	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Small intestinal perforation	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Stomatitis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Upper gastrointestinal haemorrhage	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Vomiting	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
General disorders
Chest pain	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Condition aggravated	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
General physical health deterioration	4/239 (1.7%)		3/241 (1.2%)		7/480 (1.5%)
Malaise	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Multiple organ dysfunction syndrome	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Non-cardiac chest pain	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Oedema peripheral	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Pyrexia	19/239 (7.9%)		18/241 (7.5%)		37/480 (7.7%)
Hepatobiliary disorders
Bile duct stone	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cholangitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Cholecystitis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cholelithiasis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Cholestasis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Hepatic failure	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Hepatotoxicity	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Immune system disorders
Acute graft versus host disease	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Acute graft versus host disease in skin	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Allergy to arthropod bite	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Allergy to immunoglobulin therapy	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Graft versus host disease in gastrointestinal tract	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Infections and infestations
Abscess limb	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Acute sinusitis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Aspergillus infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Bacteraemia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Bacterial disease carrier	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Bacterial sepsis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Blastocystis infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Bronchitis	4/239 (1.7%)		3/241 (1.2%)		7/480 (1.5%)
Bronchopulmonary aspergillosis	1/239 (0.4%)		5/241 (2.1%)		6/480 (1.3%)
Campylobacter colitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Campylobacter gastroenteritis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cellulitis	2/239 (0.8%)		5/241 (2.1%)		7/480 (1.5%)
Chronic sinusitis	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Cytomegalovirus infection	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Cytomegalovirus viraemia	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Device related infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Device related sepsis	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Diarrhoea infectious	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Endocarditis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Endocarditis enterococcal	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Enterobacter bacteraemia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Enterobacter sepsis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Enterococcal sepsis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Enterocolitis viral	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Epididymitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Epiglottitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Escherichia sepsis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Gastroenteritis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Gastroenteritis viral	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Gastrointestinal fungal infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Genital herpes	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
H1N1 influenza	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Hepatitis B	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Herpes simplex	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Herpes virus infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Herpes zoster	3/239 (1.3%)		4/241 (1.7%)		7/480 (1.5%)
Herpes zoster disseminated	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Herpes zoster oticus	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Influenza	4/239 (1.7%)		1/241 (0.4%)		5/480 (1%)
Intervertebral discitis	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
JC virus infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Klebsiella bacteraemia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Leishmaniasis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Listeria sepsis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Listeriosis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Localised infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Lower respiratory tract infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Lung infection	5/239 (2.1%)		3/241 (1.2%)		8/480 (1.7%)
Meningitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Meningitis bacterial	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Meningitis pneumococcal	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Mucormycosis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Mycobacterial infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Neuroborreliosis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Neutropenic sepsis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Nocardiosis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Oral candidiasis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Oral herpes	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Otitis media	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Otitis media acute	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Parvovirus infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Periorbital cellulitis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Perirectal abscess	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Pharyngitis	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Pneumococcal bacteraemia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Pneumococcal sepsis	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Pneumocystis jirovecii pneumonia	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Pneumonia	37/239 (15.5%)		35/241 (14.5%)		72/480 (15%)
Pneumonia bacterial	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pneumonia pseudomonal	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pneumonia streptococcal	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Pneumonia viral	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Post procedural cellulitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Post procedural infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Post procedural pneumonia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Post procedural sepsis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Postoperative abscess	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Progressive multifocal leukoencephalopathy	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pseudomonas infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pulmonary sepsis	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Respiratory tract infection	4/239 (1.7%)		4/241 (1.7%)		8/480 (1.7%)
Sepsis	8/239 (3.3%)		5/241 (2.1%)		13/480 (2.7%)
Septic shock	5/239 (2.1%)		3/241 (1.2%)		8/480 (1.7%)
Sinusitis	3/239 (1.3%)		2/241 (0.8%)		5/480 (1%)
Skin infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Soft tissue infection	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Staphylococcal infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Staphylococcal sepsis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Streptococcal sepsis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Upper respiratory tract infection	4/239 (1.7%)		2/241 (0.8%)		6/480 (1.3%)
Urinary tract infection	3/239 (1.3%)		5/241 (2.1%)		8/480 (1.7%)
Varicella	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Varicella zoster virus infection	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Viral infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Wound infection	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Injury, poisoning and procedural complications
Allergic transfusion reaction	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Dislocation of vertebra	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Face injury	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Fall	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Femoral neck fracture	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Femur fracture	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Hip fracture	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Humerus fracture	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Muscle strain	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Pelvic fracture	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Rib fracture	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Subdural haematoma	3/239 (1.3%)		3/241 (1.2%)		6/480 (1.3%)
Upper limb fracture	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Wound secretion	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Investigations
Alanine aminotransferase increased	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Arthroscopy	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Calcium ionised increased	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Capillary permeability increased	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Heart rate irregular	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Hepatic enzyme increased	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
International normalised ratio increased	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Platelet count decreased	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Metabolism and nutrition disorders
Dehydration	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Diabetes mellitus inadequate control	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Electrolyte imbalance	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Glucose tolerance impaired	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Hypercalcaemia	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Hypermetabolism	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Hypokalaemia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Arthritis	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Back pain	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Flank pain	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Lumbar spinal stenosis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Myalgia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Osteoporotic fracture	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Rheumatoid arthritis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Adenocarcinoma gastric	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Adenocarcinoma of colon	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Anaplastic large cell lymphoma T- and null-cell types	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Basal cell carcinoma	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Bladder cancer	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Brain neoplasm malignant	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Chronic lymphocytic leukaemia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Diffuse large B-cell lymphoma	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Endometrial adenocarcinoma	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Extraskeletal myxoid chondrosarcoma	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Gastrointestinal carcinoma	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Hodgkin's disease	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Invasive ductal breast carcinoma	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Lung adenocarcinoma metastatic	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Lung neoplasm malignant	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Malignant melanoma	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Metastases to central nervous system	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Metastases to liver	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Metastatic squamous cell carcinoma	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Myelodysplastic syndrome	2/239 (0.8%)		2/241 (0.8%)		4/480 (0.8%)
Neoplasm malignant	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Neuroendocrine carcinoma of the skin	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Non-small cell lung cancer	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Pancreatic carcinoma	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Prostate cancer	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Rectal cancer	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Refractory anaemia with an excess of blasts	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Renal neoplasm	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Richter's syndrome	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Skin cancer	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Small cell lung cancer	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Spinal meningioma benign	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Squamous cell carcinoma of skin	3/239 (1.3%)		1/241 (0.4%)		4/480 (0.8%)
T-cell lymphoma	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Tongue neoplasm malignant stage unspecified	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Nervous system disorders
Brain oedema	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Carotid artery stenosis	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cerebral haemorrhage	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cerebrovascular accident	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Depressed level of consciousness	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Generalised tonic-clonic seizure	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Headache	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Paraparesis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Polyneuropathy	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Syncope	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Toxic neuropathy	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Transient ischaemic attack	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Product Issues
Device dislocation	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Psychiatric disorders
Aggression	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Anxiety	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Confusional state	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Delirium	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Depression	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Psychomotor retardation	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Renal and urinary disorders
Acute kidney injury	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Chronic kidney disease	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Haematuria	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Nephrotic syndrome	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Renal failure	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Renal impairment	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Endometrial hyperplasia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Prostatitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Alveolitis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Asphyxia	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Bronchiectasis	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Chronic obstructive pulmonary disease	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Cough	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Dyspnoea	2/239 (0.8%)		4/241 (1.7%)		6/480 (1.3%)
Epistaxis	2/239 (0.8%)		2/241 (0.8%)		4/480 (0.8%)
Hiccups	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Hypoxia	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Interstitial lung disease	2/239 (0.8%)		0/241 (0%)		2/480 (0.4%)
Lung disorder	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pleural effusion	1/239 (0.4%)		1/241 (0.4%)		2/480 (0.4%)
Pneumonia aspiration	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pneumonitis	1/239 (0.4%)		2/241 (0.8%)		3/480 (0.6%)
Pulmonary alveolar haemorrhage	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Pulmonary embolism	2/239 (0.8%)		2/241 (0.8%)		4/480 (0.8%)
Pulmonary oedema	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Respiratory arrest	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Respiratory disorder	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Respiratory failure	0/239 (0%)		2/241 (0.8%)		2/480 (0.4%)
Skin and subcutaneous tissue disorders
Blister	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Erythema multiforme	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Skin lesion	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Surgical and medical procedures
Allogenic bone marrow transplantation therapy	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Cataract operation	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Mastectomy	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Nasal septal operation	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Vascular disorders
Aortic stenosis	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Deep vein thrombosis	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Haematoma	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Hypertension	0/239 (0%)		1/241 (0.4%)		1/480 (0.2%)
Peripheral artery aneurysm	2/239 (0.8%)		1/241 (0.4%)		3/480 (0.6%)
Venoocclusive disease	1/239 (0.4%)		0/241 (0%)		1/480 (0.2%)
Other (Not Including Serious) Adverse Events
	Ofatumumab		Observation		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	202/239 (84.5%)		139/241 (57.7%)		341/480 (71%)
Blood and lymphatic system disorders
Neutropenia	61/239 (25.5%)		22/241 (9.1%)		83/480 (17.3%)
Thrombocytopenia	13/239 (5.4%)		11/241 (4.6%)		24/480 (5%)
Gastrointestinal disorders
Constipation	13/239 (5.4%)		11/241 (4.6%)		24/480 (5%)
Diarrhoea	41/239 (17.2%)		13/241 (5.4%)		54/480 (11.3%)
Nausea	13/239 (5.4%)		8/241 (3.3%)		21/480 (4.4%)
General disorders
Fatigue	33/239 (13.8%)		22/241 (9.1%)		55/480 (11.5%)
Oedema peripheral	12/239 (5%)		10/241 (4.1%)		22/480 (4.6%)
Pyrexia	41/239 (17.2%)		23/241 (9.5%)		64/480 (13.3%)
Immune system disorders
Hypogammaglobulinaemia	12/239 (5%)		2/241 (0.8%)		14/480 (2.9%)
Infections and infestations
Bronchitis	21/239 (8.8%)		17/241 (7.1%)		38/480 (7.9%)
Herpes zoster	14/239 (5.9%)		8/241 (3.3%)		22/480 (4.6%)
Influenza	16/239 (6.7%)		10/241 (4.1%)		26/480 (5.4%)
Nasopharyngitis	22/239 (9.2%)		22/241 (9.1%)		44/480 (9.2%)
Pneumonia	17/239 (7.1%)		11/241 (4.6%)		28/480 (5.8%)
Respiratory tract infection	17/239 (7.1%)		15/241 (6.2%)		32/480 (6.7%)
Rhinitis	14/239 (5.9%)		4/241 (1.7%)		18/480 (3.8%)
Sinusitis	22/239 (9.2%)		9/241 (3.7%)		31/480 (6.5%)
Upper respiratory tract infection	52/239 (21.8%)		26/241 (10.8%)		78/480 (16.3%)
Injury, poisoning and procedural complications
Infusion related reaction	42/239 (17.6%)		0/241 (0%)		42/480 (8.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/239 (8.4%)		12/241 (5%)		32/480 (6.7%)
Back pain	15/239 (6.3%)		12/241 (5%)		27/480 (5.6%)
Nervous system disorders
Headache	23/239 (9.6%)		7/241 (2.9%)		30/480 (6.3%)
Psychiatric disorders
Insomnia	14/239 (5.9%)		6/241 (2.5%)		20/480 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	58/239 (24.3%)		28/241 (11.6%)		86/480 (17.9%)
Skin and subcutaneous tissue disorders
Pruritus	23/239 (9.6%)		9/241 (3.7%)		32/480 (6.7%)
Rash	26/239 (10.9%)		10/241 (4.1%)		36/480 (7.5%)

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.

Results Point of Contact

Name/Title	Clinical Disclosure Office
Organization	Novartis Pharmaceuticals
Phone	862-778-8300
Email	Novartis.email@novartis.com

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01039376

Other Study ID Numbers:

112517
COMB157C2301

First Posted:

Dec 25, 2009

Last Update Posted:

Jul 30, 2019

Last Verified:

Jul 1, 2019