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Clinical Trial Results:
An Open-Label, Multicenter, Randomized, Phase III Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine + RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin’s Lymphoma

Summary
EudraCT number	2009-015504-25
Trial protocol	CZ BE AT DE FR IT GB ES SE NL
Global end of trial date	30 Nov 2018

Results information
Results version number	v2(current)
This version publication date	18 Dec 2019
First version publication date	12 Oct 2016
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GO01297

ISRCTN number

US NCT number

NCT01059630

WHO universal trial number (UTN)

Other trial identifiers

Genentech Study ID:: GAO4753g

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

30 Nov 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Nov 2018

Was the trial ended prematurely?

Main objective of the trial

This is a Phase III, open-label, multicenter, randomized study to investigate the efficacy and safety of obinutuzumab (RO5072759, GA101) combined with bendamustine compared with bendamustine alone in participants with rituximab-refractory, Indolent non-Hodgkin lymphoma (iNHL).

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Apr 2010

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety

Long term follow-up duration

48 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 5

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Canada: 98

Country: Number of subjects enrolled

Switzerland: 2

Country: Number of subjects enrolled

Czech Republic: 34

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

France: 81

Country: Number of subjects enrolled

United Kingdom: 30

Country: Number of subjects enrolled

Italy: 17

Country: Number of subjects enrolled

Netherlands: 18

Country: Number of subjects enrolled

Russian Federation: 24

Country: Number of subjects enrolled

Sweden: 14

Country: Number of subjects enrolled

United States: 69

Worldwide total number of subjects

413

EEA total number of subjects

220

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

228

From 65 to 84 years

181

85 years and over

Subject disposition

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Recruitment details

Screening details

Overall, the ITT population in this final analysis comprised of 413 patients with iNHL (209 patients in the benda arm and 204 patients in the G-benda arm).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Bendamustine alone

Arm description

Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Arm type

Active comparator

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Obinutuzumab + Bendamustine

Arm description

Induction phase: Participants received Bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants. Participants also received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6. Maintenance phase: Participants with CR, PR or SD then received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first).

Arm type

Experimental

Investigational medicinal product name

Obinutuzumab

Investigational medicinal product code

Other name

RO5072759, GA101

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received obinutuzumab 1000 mg IV infusion on Days 1, 8, and 15 of Cycle 1; Day 1 of Cycles 2-6 during induction phase and 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first) during maintenance phase

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received bendamustine 90 mg/m^2 IV on Days 2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2-6 (28-day cycles) for the first 10 participants and on Days 1 and 2 of each 28-day cycle for Cycles 1-6 for remaining participants.

Number of subjects in period 1	Bendamustine alone	Obinutuzumab + Bendamustine
Started	209	204
Completed	0	0
Not completed	209	204
Physician decision	2	4
Consent withdrawn by subject	21	14
Study terminated by Sponsor	82	101
Death	100	84
Lost to follow-up	4	1

Baseline characteristics

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Reporting group title

Bendamustine alone

Reporting group description

Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Reporting group title

Obinutuzumab + Bendamustine

Reporting group description

Reporting group values	Bendamustine alone	Obinutuzumab + Bendamustine	Total
Number of subjects	209	204	413
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	113	115	228
From 65-84 years	94	87	181
85 years and over	2	2	4
Age Continuous
Units: Years
arithmetic mean (standard deviation)	61.9 ± 11.5	62.0 ± 11.3	-
Sex: Female, Male
Units: Subjects
Female	87	88	175
Male	122	116	238
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	5	6	11
Not Hispanic or Latino	174	183	357
Not Stated	30	15	45
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	2	1	3
Asian	3	6	9
Black or African American	3	5	8
Multiple	1	0	1
Unknown	19	12	31
White	181	180	361

End points

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Reporting group title

Bendamustine alone

Reporting group description

Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Reporting group title

Obinutuzumab + Bendamustine

Reporting group description

Primary: Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death

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End point title

Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death ^[1]

End point description

PD was assessed by an IRC according to the modified response criteria for indolent Non-Hodgkin's Lymphoma (iNHL) (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50 percent (%) increase from nadir in the sum of product diameter (SPD) of any previously involved nodes, or in a single involved node, or the size of other lesions (example: splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of less than (<) 1.0 cm must increase by greater than or equal to (≥) 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node greater than (>) 1 cm in its short axis.

End point type

Primary

End point timeframe

Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cycle [Cy] 4 Day 1 [1 Cy=28days], 28−42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall])

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were done for this endpoint.

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: participants	125	87

No statistical analyses for this end point

Primary: Progression-Free Survival (PFS) as Assessed by IRC

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End point title

Progression-Free Survival (PFS) as Assessed by IRC

End point description

PFS was defined as time from randomization to first occurrence of PD or death as assessed by an IRC according to modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions (e.g., splenic or hepatic nodules). To be PD, a lymph node with a diameter of short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in long axis; at least a 50% increase in longest diameter of any single previously identified node >1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% confidence interval (CI) for median was computed using method of Brookmeyer and Crowley. 9999 = non-estimable number due to higher (>50%) number of censored participants.

End point type

Primary

End point timeframe

Baseline until PD or death, whichever occurred first (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28−42 days after Cy 6 Day 1, then every 3 months up to 2 years and every 6 months for next 2 years [up to 4.5 years overall])

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: months
median (confidence interval 95%)	14.1 (11.7 to 16.6)	29.2 (20.5 to 9999)

PFS as assessed by IRC analysis

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0.7

Secondary: Number of Participants With PD or Death as Assessed by Investigator

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End point title

Number of Participants With PD or Death as Assessed by Investigator

End point description

PD was assessed by an investigator according to the modified response criteria for iNHL (Modified Cheson et al, 2007). PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to 8.5 years overall))

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: participants	152	132

No statistical analyses for this end point

Secondary: PFS as Assessed by Investigator

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End point title

PFS as Assessed by Investigator

End point description

PFS was defined as the time from randomization to the first occurrence of PD as assessed by an investigator according to the modified response criteria for iNHL (Modified Cheson et al, 2007), or death from any cause on study. PD was defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules). To be considered PD, a lymph node with a diameter of the short axis of <1.0 cm must increase by ≥ 50% and to a size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in the long axis; at least a 50% increase in the longest diameter of any single previously identified node >1 cm in its short axis. PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to 8.5 years overall)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: months
median (confidence interval 95%)	14.1 (12.6 to 16.2)	25.8 (20.1 to 36.5)

PFS as assessed by Investigator analysis

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

0.73

Secondary: Percentage of Participants With Objective Response as Assessed by IRC

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End point title

Percentage of Participants With Objective Response as Assessed by IRC

End point description

Objective response was defined as having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. IRC review was performed up clinical cutoff date of to 1 May 2015.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)	77.5 (71.24 to 82.98)	75.5 (69.00 to 81.23)

Percentage of Participants With OR

Statistical analysis description

Statistical analysis for IRC assessment.

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

= 0.9298

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.65

Secondary: Percentage of Participants With Objective Response as Assessed by Investigator

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End point title

Percentage of Participants With Objective Response as Assessed by Investigator

End point description

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)	83.3 (77.49 to 88.05)	82.4 (76.42 to 87.32)

Percentage of Participants With OR

Statistical analysis description

Statistical analysis for investigator assessment.

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

= 0.7857

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.44

upper limit

6.64

Secondary: Percentage of Participants with Best Overall Response (BOR) as Assessed by IRC

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End point title

Percentage of Participants with Best Overall Response (BOR) as Assessed by IRC

End point description

BOR observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease & disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by baseline scan & no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic & hepatic nodules, involvement of other organs is usually assessable & no measurable disease should be present, SD: Failing to attain criteria needed for a CR/PR, but not fulfilling those for PD, PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions (e.g., splenic or hepatic nodules). IRC review was performed up clinical cutoff date of to 1 May 2015.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)
IRC Assessment: CR	17.2 (12.37 to 23.04)	16.2 (11.40 to 21.96)
IRC Assessment: PR	60.3 (53.31 to 66.97)	59.3 (52.23 to 66.12)
IRC Assessment: SD	12.0 (7.89 to 17.15)	13.7 (9.32 to 19.22)
IRC Assessment: PD	5.7 (3.00 to 9.81)	4.9 (2.38 to 8.83)
IRC Assessment: Unable to evaluate	1.0 (0.12 to 3.41)	1.0 (0.12 to 3.50)
IRC Assessment: Missing	3.8 (1.67 to 7.40)	4.9 (2.38 to 8.83)

No statistical analyses for this end point

Secondary: Percentage of Participants with Best Overall Response (BOR) as Assessed by Investigator

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End point title

Percentage of Participants with Best Overall Response (BOR) as Assessed by Investigator

End point description

BOR: best response for a participant, observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present, SD: Failing to attain the criteria needed for a CR or PR, but not fulfilling those for PD, PD: appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in single involved node, or the size of other lesions (e.g., splenic or hepatic nodules).

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)
Investigator Assessment: CR	21.5 (16.16 to 27.73)	23.5 (17.89 to 29.96)
Investigator Assessment: PR	61.7 (54.76 to 68.34)	58.8 (51.74 to 65.65)
Investigator Assessment: SD	6.7 (3.71 to 10.98)	6.4 (3.44 to 10.65)
Investigator Assessment: PD	4.8 (2.32 to 8.62)	6.4 (3.44 to 10.65)
Investigator Assessment: Unable to evaluate	1.4 (0.30 to 4.14)	0.5 (0.01 to 2.70)
Investigator Assessment: Missing	3.8 (1.67 to 7.40)	4.4 (2.04 to 8.21)

No statistical analyses for this end point

Secondary: Percentage of Participants with BOR at the End of induction Treatment as Assessed by IRC

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End point title

Percentage of Participants with BOR at the End of induction Treatment as Assessed by IRC

End point description

BOR observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease & disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan & no new sites; no increase in size of other nodes, liver or spleen; with exception of splenic & hepatic nodules, involvement of other organs is usually assessable & no measurable disease should be present, SD: Failing to attain criteria needed for a CR/PR, but not fulfilling those for PD, PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or size of other lesions (e.g., splenic/hepatic nodules). IRC review was performed up clinical cutoff date of to 1 May 2015.

End point type

Secondary

End point timeframe

Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28−42 days after Cy 6 Day 1)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)
IRC Assessment: CR	12.0 (7.93 to 17.23)	11.8 (7.69 to 17.00)
IRC Assessment: PR	52.4 (45.38 to 59.35)	54.9 (47.80 to 61.86)
IRC Assessment: SD	10.1 (6.36 to 15.02)	11.8 (7.69 to 17.00)
IRC Assessment: PD	10.6 (6.75 to 15.58)	8.8 (5.31 to 13.59)
IRC Assessment: Unable to Evaluate	2.9 (1.07 to 6.17)	2.0 (0.54 to 4.94)
IRC Assessment: Missing	12.0 (7.93 to 17.23)	10.8 (6.88 to 15.87)

No statistical analyses for this end point

Secondary: Percentage of Participants with BOR at the End of induction Treatment as Assessed by Investigator

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End point title

Percentage of Participants with BOR at the End of induction Treatment as Assessed by Investigator

End point description

BOR: best response for a participant, observed during assessment period according to modified response criteria for iNHL (Modified Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present, SD: Failing to attain criteria needed for a CR or PR, but not fulfilling those for PD, PD: appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in the SPD of any previously involved nodes, or in a single involved node, or the size of other lesions (e.g., splenic or hepatic nodules).

End point type

Secondary

End point timeframe

Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28−42 days after Cy 6 Day 1)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)
Investigator Assessment: CR	15.8 (11.12 to 21.45)	17.2 (12.25 to 23.04)
Investigator Assessment: PR	53.1 (46.10 to 60.03)	60.3 (53.23 to 67.06)
Investigator Assessment: SD	4.3 (1.99 to 8.02)	3.9 (1.71 to 7.58)
Investigator Assessment: PD	12.0 (7.89 to 17.15)	9.3 (5.70 to 14.16)
Investigator Assessment: Unable to Evaluate	2.9 (1.06 to 6.14)	0.5 (0.01 to 2.70)
Investigator Assessment: Missing	12.0 (7.89 to 17.15)	8.8 (5.31 to 13.59)

No statistical analyses for this end point

Secondary: Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC

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End point title

Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC

End point description

End point type

Secondary

End point timeframe

Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28−42 days after Cy 6 Day 1)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)	64.4 (57.51 to 70.92)	66.7 (59.75 to 73.10)

OR at the End of Induction Treatment

Statistical analysis description

Statistical analysis for IRC assessment.

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

= 0.8347

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

2.24

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

11.69

Secondary: Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator

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End point title

Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator

End point description

End point type

Secondary

End point timeframe

Baseline until end of induction treatment (assessed at baseline, 14 days prior to Cy 4 Day 1 [1 Cy=28days], 28−42 days after Cy 6 Day 1)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: percentage of participants
number (confidence interval 95%)	68.9 (62.15 to 75.11)	77.5 (71.09 to 82.99)

OR at End of Induction Treatment

Statistical analysis description

Statistical analysis for investigator assessment.

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0466

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

8.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

17.32

Secondary: Duration of Response (DoR) as Assessed by IRC

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End point title

Duration of Response (DoR) as Assessed by IRC

End point description

DoR: time from first objective response of CR/PR to first occurrence of PD/relapse/death from any cause. CR: Complete disappearance of all detectable evidence of disease & disease-related symptoms if present before therapy. PR: at least 50% measurable disease regressed vs. to baseline scan and no new sites; no increase in size of other nodes/liver/spleen; other organs involved is usually assessable; no measurable disease present. PD: any new lesion >1.5 cm in any axis appear during or at end of therapy, even if other lesions are decreasing in size; at least 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions. DoR estimated using Kaplan-Meier method. IRC review performed up to clinical cutoff date 1 May 2015. 9999 = non-estimable number due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	165	158
Units: months
median (confidence interval 95%)	12.7 (10.4 to 14.1)	38.5 (25.4 to 9999)

Duration of Response

Statistical analysis description

Randomization was stratified for iNHL subtype (follicular versus other), refractory type (rituximab monotherapy versus rituximab + chemotherapy), number of prior therapies (less than or equal to 2 versus greater than 2) and geographic region.

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

323

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

0.61

Secondary: Duration of Response (DoR) as Assessed by Investigator

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End point title

Duration of Response (DoR) as Assessed by Investigator

End point description

DoR: time from first objective response of CR/PR to first occurrence of PD/relapse/death from any cause. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. PR: at least 50% regression of measurable disease compared to baseline scan and no new sites; no increase in size of other nodes, liver, or spleen; with exception of splenic, hepatic nodules; involvement of other organs is usually assessable; no presence of measurable disease. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least 50% increase from nadir in SPD of any previously involved nodes, or in single involved node, or size of other lesions. DoR was estimated using Kaplan-Meier method.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	176	172
Units: months
median (confidence interval 95%)	12.7 (11.1 to 15.5)	32.3 (20.8 to 39.0)

Duration of Response

Statistical analysis description

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

0.67

Secondary: Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC

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End point title

Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC

End point description

DFS was defined as time from first occurrence of a documented CR until progression on basis of IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]) or death from any cause on study. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. DFS was estimated using Kaplan-Meier method. IRC review was performed up clinical cutoff date of to 1 May 2015. 9999 = non-estimable number due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	37	46
Units: months
median (confidence interval 95%)	13.2 (8.5 to 9999)	9999 (9999 to 9999)

Disease Free Survival

Statistical analysis description

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

0.45

Secondary: Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator

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End point title

Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator

End point description

DFS was defined as the time from the first occurrence of a documented CR until progression on the basis of the IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]) or death from any cause on study. CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. DFS was estimated using Kaplan-Meier method.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 8.5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	50	70
Units: months
median (confidence interval 95%)	20.0 (8.6 to 31.0)	36.0 (26.6 to 68.2)

Disease Free Survival

Statistical analysis description

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

0.81

Secondary: Event-free Survival (EFS) as Assessed by IRC

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End point title

Event-free Survival (EFS) as Assessed by IRC

End point description

EFS was defined as the time between the date of randomization and the date of PD/relapse based on IRC assessments (as per modified response criteria for iNHL [Modified Cheson et al, 2007]), death from any cause on study, or start of a new anti-lymphoma therapy. PD: appearance of any new lesion >1.5 cm in any axis during or at end of therapy, even if other lesions are decreasing in size; at least a 50% increase from nadir in SPD of any previously involved nodes, or in a single involved node, or size of other lesions. EFS was estimated using Kaplan-Meier method. IRC review was performed up clinical cutoff date of to 1 May 2015.

End point type

Secondary

End point timeframe

Baseline until PD or death, whichever occurred first (up to approximately 5 years)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: months
median (confidence interval 95%)	13.7 (11.4 to 15.5)	25.3 (13.9 to 35.0)

Event-Free Survival

Statistical analysis description

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

0.74

Secondary: Percentage of Participants Who Died

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End point title

Percentage of Participants Who Died

End point description

End point type

Secondary

End point timeframe

Baseline until death (up to 8.5 years overall)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	203	204
Units: percentage of participants
number (not applicable)	49.3	41.2

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

OS was defined as the time between the date of randomization and the date of death from any cause. OS was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley. 9999 = non-estimable number due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

Baseline until death (up to 8.5 years overall)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: months
median (confidence interval 95%)	65.6 (48.5 to 87.8)	88.3 (71.1 to 9999)

Overall Survival

Statistical analysis description

Comparison groups

Bendamustine alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

413

Analysis specification

Pre-specified

Analysis type

P-value

= 0.081

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.03

Secondary: Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score

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End point title

Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score

End point description

The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Physical Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for physical well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better participant-reported outcome (PRO)/quality of life (QoL). In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=187, n=187)	22.58 ± 5.23	22.76 ± 4.61
CFB at Cycle 3 Day 1 (n=156, n=154)	-1.56 ± 5.49	-0.69 ± 4.06
CFB at Cycle 4 Day 1 (n=5, n=2)	-6.80 ± 4.21	-3.00 ± 2.83
CFB at Cycle 5 Day 1 (n=142, n=145)	-1.82 ± 5.06	-0.72 ± 4.16
CFB at End of Induction Treatment (n=149, n=142)	-1.00 ± 5.14	-0.61 ± 4.62
CFB at Follow-up Month 2 (n=108, n=133)	0.62 ± 5.14	0.58 ± 4.45
CFB at Follow-up Month 4 (n=95, n=121)	0.53 ± 4.58	0.88 ± 4.47
CFB at Follow-up Month 6 (n=77, n=112)	0.29 ± 3.74	0.91 ± 3.82
CFB at Follow-up Month 8 (n=75, n=104)	-0.01 ± 3.53	0.87 ± 3.96
CFB at Follow-up Month 10 (n=58, n=91)	0.06 ± 4.16	0.56 ± 3.81
CFB at Follow-up Month 12 (n=53, n=90)	0.26 ± 4.02	0.74 ± 4.24
CFB at Follow-up Month 14 (n=46, n=85)	0.03 ± 4.14	0.71 ± 3.94
CFB at Follow-up Month 16 (n=42, n=82)	-0.10 ± 3.49	1.31 ± 3.68
CFB at Follow-up Month 18 (n=41, n=76)	-0.22 ± 3.64	0.92 ± 3.99
CFB at Follow-up Month 20 (n=34, n=73)	-0.36 ± 3.70	0.74 ± 3.69
CFB at Follow-up Month 22 (n=29, n=71)	-0.25 ± 3.93	0.40 ± 4.47
CFB at Follow-up Month 24 (n=30, n=68)	-0.77 ± 4.16	0.52 ± 4.42
CFB at Final Follow-up (n=86, n=106)	0.16 ± 4.17	0.22 ± 4.47
CFB at Extension Follow-up Month 6 (n=21, n=60)	0.36 ± 3.48	0.57 ± 4.71
CFB at Extension Follow-up Month 18 (n=19, n=46)	0.80 ± 2.54	1.19 ± 4.98
CFB at Extension Follow-up Month 24 (n=18, n=39)	1.53 ± 5.96	0.56 ± 5.26

No statistical analyses for this end point

Secondary: CFB in FACT-Lym-Social/Family Well-being Sub-scale Score

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End point title

CFB in FACT-Lym-Social/Family Well-being Sub-scale Score

End point description

The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Social/family Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for social/family well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycle 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=186, n=191)	22.04 ± 5.65	22.14 ± 5.51
CFB at Cycle 3 Day 1 (n=155, n=158)	-0.21 ± 3.59	-0.10 ± 3.87
CFB at Cycle 4 Day 1 (n=5, n=3)	-1.00 ± 3.67	3.11 ± 2.83
CFB at Cycle 5 Day 1 (n=141, n=149)	-0.34 ± 4.32	-0.34 ± 4.33
CFB at End of Induction Treatment (n=147, n=145)	-0.65 ± 5.21	-0.88 ± 3.60
CFB at Follow-up Month 2 (n=106, n=137)	-0.02 ± 4.83	-0.57 ± 5.37
CFB at Follow-up Month 4 (n=94, n=125)	0.27 ± 4.65	-0.26 ± 5.02
CFB at Follow-up Month 6 (n=76, n=114)	0.05 ± 4.46	-0.08 ± 4.64
CFB at Follow-up Month 8 (n=209, n=204)	-0.68 ± 3.67	-0.37 ± 4.99
CFB at Follow-up Month 10 (n=58, n=94)	0.56 ± 5.00	0.13 ± 5.14
CFB at Follow-up Month 12 (n=53, n=93)	0.06 ± 5.89	-0.47 ± 5.64
CFB at Follow-up Month 14 (n=45, n=89)	0.56 ± 3.28	-0.03 ± 4.16
CFB at Follow-up Month 16 (n=42, n=85)	0.36 ± 6.79	-0.15 ± 5.28
CFB at Follow-up Month 18 (n=41, n=78)	0.44 ± 6.23	0.04 ± 5.35
CFB at Follow-up Month 20 (n=34, n=76)	-0.66 ± 4.28	0.00 ± 5.75
CFB at Follow-up Month 22 (n=29, n=74)	0.29 ± 7.12	-0.50 ± 5.02
CFB at Follow-up Month 24 (n=30, n=71)	-1.29 ± 3.91	-0.41 ± 5.24
CFB at Final Follow-up (n=86, n=109)	-0.19 ± 4.91	-0.52 ± 5.56
CFB at Extension Follow-up Month 6 (n=21, n=63)	-0.35 ± 2.49	-0.16 ± 4.92
CFB at Extension Follow-up Month 18 (n=18, n=49)	-0.15 ± 2.92	0.71 ± 5.26
CFB at Extension Follow-up Month 24 (n=18, n=40)	-0.41 ± 3.18	0.44 ± 5.02

No statistical analyses for this end point

Secondary: CFB in FACT-Lym-Emotional Well-Being Sub-scale Score

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End point title

CFB in FACT-Lym-Emotional Well-Being Sub-scale Score

End point description

The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Emotional Well-being sub-scale includes 6 items measured on 0-4 point scale. The total score for emotional well-being sub-scale is sum of each 6 items (range: 0-24). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=189, n=193)	17.38 ± 4.45	17.81 ± 4.33
CFB at Cycle 1 Day 1 (n=0, n=0)	0 ± 0	0 ± 0
CFB at Cycle 3 Day 1 (n=157, n=163)	0.61 ± 3.04	0.78 ± 3.14
CFB at Cycle 4 Day 1 (n=5, n=3)	-0.60 ± 3.85	3.40 ± 4.42
CFB at Cycle 5 Day 1 (n=143, n=152)	0.37 ± 3.08	0.50 ± 3.52
CFB at End of Induction Treatment (n=149, n=145)	0.53 ± 3.57	0.59 ± 4.03
CFB at Follow-up Month 2 (n=107, n=138)	0.66 ± 3.89	0.67 ± 3.83
CFB at Follow-up Month 4 (n=96, n=124)	1.34 ± 3.54	0.95 ± 3.51
CFB at Follow-up Month 6 (n=78, n=116)	0.89 ± 3.57	0.96 ± 3.44
CFB at Follow-up Month 8 (n=76, n=108)	0.26 ± 3.35	0.97 ± 3.34
CFB at Follow-up Month 10 (n=58, n=94)	0.69 ± 3.31	1.32 ± 3.23
CFB at Follow-up Month 12 (n=54, n=93)	-0.07 ± 3.88	0.95 ± 3.29
CFB at Follow-up Month 14 (n=47, n=89)	0.46 ± 3.22	1.07 ± 3.82
CFB at Follow-up Month 16 (n=43, n=86)	0.13 ± 3.87	1.04 ± 3.69
CFB at Follow-up Month 18 (n=41, n=79)	0.42 ± 3.36	1.00 ± 3.38
CFB at Follow-up Month 20 (n=35, n=76)	-0.43 ± 2.90	0.94 ± 4.28
CFB at Follow-up Month 22 (n=30, n=74)	0.18 ± 2.81	0.97 ± 3.79
CFB at Follow-up Month 24 (n=31, n=71)	0.06 ± 3.20	1.12 ± 3.78
CFB at Final Follow-up (n=84, n=111)	0.38 ± 3.77	0.34 ± 4.37
CFB at Extension Follow-up Month 6 (n=23, n=63)	-0.44 ± 3.26	0.39 ± 3.99
CFB at Extension Follow-up Month 18 (n=20, n=50)	-0.08 ± 3.80	0.75 ± 3.85
CFB at Extension Follow-up Month 24 (n=19, n=42)	1.04 ± 4.16	0.97 ± 4.36

No statistical analyses for this end point

Secondary: CFB in FACT-Lym-Functional Well-Being Sub-scale Score

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End point title

CFB in FACT-Lym-Functional Well-Being Sub-scale Score

End point description

The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Functional Well-being sub-scale includes 7 items measured on 0-4 point scale. The total score for functional well-being sub-scale is sum of each 7 items (range: 0-28). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 1, 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction); Extension follow-up Months 6, 18 and 24

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=189, n=196)	17.98 ± 6.31	17.90 ± 6.08
CFB at Cycle 1 Day 1 (n=0, n=0)	0 ± 0	0 ± 0
CFB at Cycle 3 Day 1 (n=157, n=165)	-0.54 ± 4.65	0.38 ± 4.66
CFB at Cycle 4 Day 1 (n=5, n=3)	-0.80 ± 2.28	1.78 ± 4.91
CFB at Cycle 5 Day 1 (n=143, n=154)	-0.71 ± 5.04	0.67 ± 5.35
CFB at End of Induction Treatment (n=150, n=147)	-0.50 ± 5.50	0.00 ± 5.25
CFB at Follow-up Month 2 (n=107, n=139)	0.31 ± 5.27	0.65 ± 5.38
CFB at Follow-up Month 4 (n=96, n=126)	0.24 ± 5.11	1.31 ± 5.86
CFB at Follow-up Month 6 (n=77, n=117)	0.95 ± 4.58	1.26 ± 5.08
CFB at Follow-up Month 8 (n=76, n=109)	-0.27 ± 4.38	0.92 ± 5.45
CFB at Follow-up Month 10 (n=59, n=96)	1.09 ± 4.25	1.00 ± 5.52
CFB at Follow-up Month 12 (n=54, n=94)	0.18 ± 5.59	1.78 ± 6.04
CFB at Follow-up Month 14 (n=47, n=90)	1.16 ± 4.27	1.22 ± 4.84
CFB at Follow-up Month 16 (n=43, n=87)	0.91 ± 3.97	1.69 ± 5.95
CFB at Follow-up Month 18 (n=41, n=79)	0.21 ± 4.12	1.84 ± 5.77
CFB at Follow-up Month 20 (n=35, n=77)	-0.27 ± 4.90	1.43 ± 6.14
CFB at Follow-up Month 22 (n=30, n=75)	-0.32 ± 5.70	0.82 ± 5.00
CFB at Follow-up Month 24 (n=31, n=71)	-0.96 ± 4.36	0.98 ± 5.87
CFB at Final Follow-up (n=84, n=114)	-0.08 ± 4.94	0.50 ± 6.19
CFB at Extension Follow-up Month 6 (n=23, n=63)	1.01 ± 3.51	0.85 ± 6.65
CFB at Extension Follow-up Month 18 (n=19, n=50)	0.96 ± 4.51	1.90 ± 6.50
CFB at Extension Follow-up Month 24 (n=19, n=42)	2.22 ± 3.34	2.62 ± 6.95

No statistical analyses for this end point

Secondary: CFB in FACT-Lym-Lymphoma Sub-scale Score

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End point title

CFB in FACT-Lym-Lymphoma Sub-scale Score

End point description

The FACT-Lym measures 5 sub-scales which includes 42 items; responses to each item range from 0, "Not at all" to 4, "Very much". Total score ranges from 0-168. Lymphoma scale includes 15 items measured on 0-4 point scale. The total score for lymphoma sub-scale is sum of each 15 items (range: 0-60). Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up). 9999 = non-applicable number

End point type

Secondary

End point timeframe

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=189, n=194)	44.79 ± 9.66	45.61 ± 9.17
CFB at Cycle 1 Day 1 (n=209, n=204)	9999 ± 9999	9999 ± 9999
CFB at Cycle 3 Day 1 (n=154, n=162)	0.98 ± 6.97	1.24 ± 5.71
CFB at Cycle 4 Day 1 (n=5, n=2)	-2.80 ± 5.76	9.50 ± 3.54
CFB at Cycle 5 Day 1 (n=142, n=151)	0.75 ± 6.79	1.41 ± 6.21
CFB at End of Induction Treatment (n=148, n=148)	1.64 ± 7.10	0.74 ± 7.89
CFB at Follow-up Month 2 (n=107, n=135)	3.44 ± 6.78	2.45 ± 6.22
CFB at Follow-up Month 4 (n=96, n=123)	2.77 ± 6.71	2.39 ± 6.54
CFB at Follow-up Month 6 (n=79, n=117)	2.33 ± 6.44	3.00 ± 7.05
CFB at Follow-up Month 8 (n=75, n=107)	1.79 ± 6.01	2.52 ± 6.69
CFB at Follow-up Month 10 (n=59 n=94)	1.90 ± 6.78	2.28 ± 6.82
CFB at Follow-up Month 12 (n=53, n=94)	2.12 ± 6.47	2.89 ± 6.42
CFB at Follow-up Month 14 (n=47, n=91)	0.48 ± 6.64	2.58 ± 6.37
CFB at Follow-up Month 16 (n=42, n=86)	0.44 ± 7.79	3.27 ± 6.14
CFB at Follow-up Month 18 (n=42, n=78)	1.18 ± 6.09	2.91 ± 6.79
CFB at Follow-up Month 20 (n=34, n=75)	0.57 ± 7.43	2.83 ± 6.41
CFB at Follow-up Month 22 (n=30, n=72)	1.89 ± 8.62	2.55 ± 6.58
CFB at Follow-up Month 24 (n=31, n=70)	0.66 ± 7.59	2.73 ± 6.48
CFB at Final Follow-up (n=85, n=112)	1.62 ± 7.17	1.33 ± 7.38
CFB at Extension Follow-up Month 6 (n=23, n=61)	0.92 ± 5.06	2.98 ± 7.22
CFB at Extension Follow-up Month 18 (n=20, n=50)	1.80 ± 8.30	2.35 ± 5.72
CFB at Extension Follow-up Month 24 (n=19, n=42)	4.89 ± 6.67	2.23 ± 6.85

No statistical analyses for this end point

Secondary: CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase

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End point title

CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase

End point description

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score; assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). For ‘Obinutuzumab + Bendamustine’ arm, participants who had their follow-up Month 2 and 4 visits before start of maintenance treatment were reported in induction phase results under “CFB at Follow-up Month 2” and “CFB at Follow-up Month 4” categories. 9999 = non-applicable number.

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 1, 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=186, 193)	0.77 ± 0.22	0.79 ± 0.20
CFB at Cycle 3 Day 1 (n=157, 161)	0.03 ± 0.21	0.00 ± 0.19
CFB at Cycle 4 Day 1 (n=5, 3)	-0.10 ± 0.23	-0.07 ± 0.41
CFB at Cycle 5 Day 1 (n=142, 153)	0.01 ± 0.21	0.02 ± 0.20
CFB at End of Induction Treatment (n=136, 140)	0.01 ± 0.22	0.01 ± 0.20
CFB at Follow-up Month 2 (n=39, 135)	0.06 ± 0.24	0.04 ± 0.18
CFB at Follow-up Month 4 (n=0, 2)	9999 ± 9999	-0.12 ± 0.00
CFB at Follow-up Month 14 (n=1, 0)	0.12 ± 9999	9999 ± 9999

No statistical analyses for this end point

Secondary: CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase

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End point title

CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase

End point description

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data for this outcome was planned to be reported only for ‘Obinutuzumab + Bendamustine’ arm. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). Follow-up months were during maintenance phase.

End point type

Secondary

End point timeframe

Baseline, Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final follow-up (up to 2 years after end of induction) (End of induction = up to Month 6)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	2	158
Units: units on a scale
arithmetic mean (standard deviation)
CFB at Follow-up Month 2 (n=0, 2)	9999 ± 9999	-0.15 ± 0.22
CFB at Follow-up Month 4 (n= 1, 119)	0.15 ± 9999	0.03 ± 0.22
CFB at Follow-up Month 6 (n= 1, 109)	0.15 ± 9999	0.04 ± 0.19
CFB at Follow-up Month 8 (n= 1, 101)	0.15 ± 9999	0.04 ± 0.21
CFB at Follow-up Month 10 (n= 1, 91)	0.15 ± 9999	0.03 ± 0.20
CFB at Follow-up Month 12 (n= 0, 87)	9999 ± 9999	0.06 ± 0.18
CFB at Follow-up Month 14 (n= 0, 80)	9999 ± 9999	0.06 ± 0.19
CFB at Follow-up Month 16 (n= 0, 78)	9999 ± 9999	0.05 ± 0.19
CFB at Follow-up Month 18 (n= 0, 73)	9999 ± 9999	0.05 ± 0.18
CFB at Follow-up Month 20 (n= 0, 69)	9999 ± 9999	0.05 ± 0.20
CFB at Follow-up Month 22 (n= 0, 69)	9999 ± 9999	0.05 ± 0.24
CFB at Follow-up Month 24 (n= 0, 64)	9999 ± 9999	0.03 ± 0.22
CFB at Final Follow-up (n= 0, 39)	9999 ± 9999	0.03 ± 0.25

No statistical analyses for this end point

Secondary: CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase

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End point title

CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase

End point description

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeter (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). For ‘Obinutuzumab + Bendamustine’ arm, participants who had their follow-up Month 2 and 4 visits before start of maintenance treatment were reported in induction phase results under “CFB at Follow-up Month 2” and “CFB at Follow-up Month 4” categories. 9999 = non-applicable number

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 3, 4, 5, End of induction treatment (up to Month 6); Follow-up Months 2, 4 and 14

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=183, 188)	69.48 ± 20.71	68.03 ± 21.69
CFB at Cycle 3 Day 1 (n=152, 153)	0.91 ± 19.38	3.32 ± 15.99
CFB at Cycle 4 Day 1 (n=5, 3)	-14.00 ± 33.29	-4.33 ± 42.15
CFB at Cycle 5 Day 1 (n=136, 141)	0.35 ± 20.79	5.17 ± 17.35
CFB at End of Induction Treatment (n=132, 135)	5.71 ± 61.88	5.82 ± 22.20
CFB at Follow-up Month 2 (n=36, 128)	5.19 ± 19.12	6.85 ± 18.95
CFB at Follow-up Month 4 (n=0, 2)	9999 ± 9999	0.00 ± 14.14
CFB at Follow-up Month 14 (n=1, 0)	10.00 ± 9999	9999 ± 9999

No statistical analyses for this end point

Secondary: CFB in EQ-5D VAS Score During Maintenance Phase

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End point title

CFB in EQ-5D VAS Score During Maintenance Phase

End point description

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Data for this outcome was planned to be reported only for ‘Obinutuzumab + Bendamustine’ arm. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction). Follow-up months were during maintenance phase. 9999 = non-calculable number

End point type

Secondary

End point timeframe

Baseline, Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up (up to 2 years after end of induction) (end of induction = up to Month 6)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	2	158
Units: units on a scale
arithmetic mean (standard deviation)
CFB at Follow-up Month 2 (n= 0, 1)	9999 ± 9999	-40.00 ± 9999
CFB at Follow-up Month 4 (n= 1, 111)	5.00 ± 9999	5.59 ± 19.61
CFB at Follow-up Month 6 (n= 1, 106)	5.00 ± 9999	6.04 ± 19.00
CFB at Follow-up Month 8 (n= 1, 95)	5.00 ± 9999	4.79 ± 17.18
CFB at Follow-up Month 10 (n= 1, 86)	-15.00 ± 9999	4.62 ± 16.28
CFB at Follow-up Month 12 (n= 0, 82)	9999 ± 9999	5.73 ± 16.04
CFB at Follow-up Month 14 (n= 0, 77)	9999 ± 9999	5.45 ± 17.36
CFB at Follow-up Month 16 (n= 0, 76)	9999 ± 9999	6.66 ± 17.44
CFB at Follow-up Month 18 (n= 0, 69)	9999 ± 9999	6.13 ± 19.44
CFB at Follow-up Month 20 (n=0, 66)	9999 ± 9999	7.56 ± 15.43
CFB at Follow-up Month 22 (n= 0, 64)	9999 ± 9999	6.97 ± 15.55
CFB at Follow-up Month 24 (n= 0, 61)	9999 ± 9999	8.28 ± 16.23
CFB at Final Follow-up (n= 0, 38)	9999 ± 9999	4.47 ± 14.91

No statistical analyses for this end point

Secondary: CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score

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End point title

CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score

End point description

The FACT-G is the sum of 4 sub-scales (physical, social, emotional and functional well-being) of FACT-Lym which includes total 27 items; responses to each item range from 0, “Not at all” to 4, “Very much”. Total score ranges from 0-108. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: Units on a scale
arithmetic mean (standard deviation)
Baseline (n=185, n=186)	79.86 ± 16.25	80.78 ± 16.27
CFB at Cycle 3 Day 1 (n=154, n=154)	-1.87 ± 12.28	0.11 ± 10.30
CFB at Cycle 4 Day 1 (n=5, n=2)	-9.37 ± 9.89	0.52 ± 4.98
CFB at Cycle 5 Day 1 (n=140, n=145)	-2.44 ± 12.01	0.06 ± 11.13
CFB at End of Induction Treatment (n=146, n=140)	-1.84 ± 13.83	-0.92 ± 11.77
CFB at Follow-up Month 2 (n=107, n=133)	1.53 ± 13.42	1.22 ± 12.01
CFB at Follow-up Month 4 (n=95, n=120)	2.55 ± 11.47	3.06 ± 13.00
CFB at Follow-up Month 6 (n=75, n=111)	2.54 ± 10.68	3.24 ± 11.40
CFB at Follow-up Month 8 (n=74, n=104)	-0.53 ± 10.15	2.49 ± 11.45
CFB at Follow-up Month 10 (n=57, n=88)	2.29 ± 11.39	3.46 ± 11.83
CFB at Follow-up Month 12 (n=53, n=90)	0.68 ± 13.16	2.82 ± 14.29
CFB at Follow-up Month 14 (n=45, n=84)	2.48 ± 9.42	2.94 ± 11.97
CFB at Follow-up Month 16 (n=42, n=82)	1.54 ± 10.61	4.09 ± 12.87
CFB at Follow-up Month 18 (n=39, n=76)	1.16 ± 11.57	4.06 ± 13.36
CFB at Follow-up Month 20 (n=33, n=73)	-1.21 ± 12.25	3.05 ± 14.29
CFB at Follow-up Month 22 (n=28, n=71)	0.64 ± 14.27	1.80 ± 12.43
CFB at Follow-up Month 24 (n=29, n=67)	-2.39 ± 9.32	2.28 ± 13.83
CFB at Final Follow-up (n=84, n=106)	0.50 ± 11.25	0.78 ± 14.94
CFB at Extension Follow Up Month 6 (n=21, n=60)	0.48 ± 8.71	1.74 ± 14.23
CFB at Extension Follow Up Month 18 (n=18, n=46)	2.29 ± 8.40	4.56 ± 15.02
CFB at Extension Follow Up Month 24 (n=18, n=38)	4.48 ± 11.10	4.47 ± 15.22

No statistical analyses for this end point

Secondary: CFB in FACT-Lym Trial Outcome Index (TOI)

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End point title

CFB in FACT-Lym Trial Outcome Index (TOI)

End point description

TOI is the sum of 3 sub-scales (physical well-being, functional well-being, and Lymphoma sub-scale) of FACT-Lym which includes total 29 items; responses to each item range from 0, “Not at all” to 4, “Very much”. Total score ranges from 0−116. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: Units on a scale
arithmetic mean (standard deviation)
Baseline (n=190, n=196)	84.66 ± 19.36	84.76 ± 18.97
CFB at Cycle 3 Day 1 (n=159, n=165)	-1.94 ± 17.96	1.81 ± 13.88
CFB at Cycle 4 Day 1 (n=5, n=3)	-10.40 ± 10.38	26.44 ± 19.51
CFB at Cycle 5 Day 1 (n=144, n=154)	-1.38 ± 15.38	2.37 ± 14.15
CFB at End of Induction Treatment (n=151, n=149)	-0.52 ± 17.23	0.40 ± 16.45
CFB at Follow-up Month 2 (n=108, n=139)	3.75 ± 15.36	4.60 ± 14.85
CFB at Follow-up Month 4 (n=96, n=127)	3.81 ± 13.39	5.18 ± 17.06
CFB at Follow-up Month 6 (n=79, n=117)	3.26 ± 12.19	6.07 ± 13.72
CFB at Follow-up Month 8 (n=76, n=109)	1.36 ± 12.39	5.36 ± 14.21
CFB at Follow-up Month 10 (n=59, n=96)	3.52 ± 13.16	4.94 ± 15.96
CFB at Follow-up Month 12 (n=54, n=95)	2.05 ± 15.14	6.13 ± 15.72
CFB at Follow-up Month 14 (n=47, n=91)	2.25 ± 11.92	5.13 ± 14.30
CFB at Follow-up Month 16 (n=43, n=87)	0.75 ± 14.15	6.78 ± 15.11
CFB at Follow-up Month 18 (n=42, n=79)	1.36 ± 11.30	7.26 ± 14.62
CFB at Follow-up Month 20 (n=35, n=77)	-0.64 ± 15.21	6.36 ± 14.99
CFB at Follow-up Month 22 (n=30, n=75)	2.26 ± 14.54	5.30 ± 17.88
CFB at Follow-up Month 24 (n=31, n=72)	-0.14 ± 13.44	5.30 ± 17.88
CFB at Final Follow-up (n=86, n=114)	0.84 ± 14.80	3.84 ± 16.22
CFB at Extension Follow Up Month 6 (n=23, n=63)	2.30 ± 10.77	5.53 ± 18.44
CFB at Extension Follow Up Month 18 (n=20, n=50)	4.02 ± 14.01	7.31 ± 15.69
CFB at Extension Follow Up Month 24 (n=19, n=42)	10.04 ± 13.35	7.07 ± 17.59

No statistical analyses for this end point

Secondary: CFB in FACT-Lym Total Score

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End point title

CFB in FACT-Lym Total Score

End point description

FACT-Lym total score is the sum of physical well-being score (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and Lymphoma sub-scale (15 items); responses to each item range from 0, “Not at all” to 4, “Very much”. Total score ranges from 0−168. Higher scores indicate a better PRO/QoL. In timeframe, follow-up months represents months after end of induction (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: Units on a scale
arithmetic mean (standard deviation)
Baseline (n=186, n=187)	124.56 ± 24.17	126.22 ± 23.98
CFB at Cycle 3 Day 1 (n=153, n=154)	-0.74 ± 17.91	1.33 ± 13.89
CFB at Cycle 4 Day 1 (n=5, n=2)	-12.16 ± 14.80	22.53 ± 16.23
CFB at Cycle 5 Day 1 (n=140, n=144)	-1.68 ± 16.61	1.71 ± 15.23
CFB at End of Induction Treatment (n=147, n=140)	0.02 ± 18.55	0.35 ± 18.29
CFB at Follow-up Month 2 (n=106, n=131)	5.10 ± 17.73	3.54 ± 15.45
CFB at Follow-up Month 4 (n=95, n=119)	5.40 ± 16.29	5.50 ± 17.76
CFB at Follow-up Month 6 (n=76, n=113)	5.03 ± 15.01	6.57 ± 15.96
CFB at Follow-up Month 8 (n=74, n=104)	1.48 ± 14.27	5.18 ± 15.61
CFB at Follow-up Month 10 (n=58, n=91)	4.58 ± 16.39	5.70 ± 16.89
CFB at Follow-up Month 12 (n=52, n=91)	2.97 ± 17.84	5.88 ± 18.93
CFB at Follow-up Month 14 (n=45, n=87)	3.18 ± 13.85	5.92 ± 17.06
CFB at Follow-up Month 16 (n=41, n=83)	2.25 ± 14.98	7.59 ± 16.97
CFB at Follow-up Month 18 (n=40, n=76)	2.16 ± 15.38	6.99 ± 18.27
CFB at Follow-up Month 20 (n=33, n=73)	-0.89 ± 16.34	5.66 ± 18.90
CFB at Follow-up Month 22 (n=29, n=71)	2.15 ± 19.03	4.59 ± 17.98
CFB at Follow-up Month 24 (n=30, n=67)	-2.13 ± 15.74	5.28 ± 18.75
CFB at Final follow-up (n=84, n=105)	2.15 ± 16.60	2.55 ± 20.11
CFB at Extension Follow Up Month 6 (n=21, n=60)	1.22 ± 11.67	5.14 ± 20.30
CFB at Extension Follow Up Month 18 (n=18, n=48)	4.92 ± 14.73	6.88 ± 19.24
CFB at Extension Follow Up Month 24 (n=18, n=41)	9.69 ± 15.88	6.13 ± 20.32

No statistical analyses for this end point

Secondary: Time to Deterioration of FACT-Lym TOI

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End point title

Time to Deterioration of FACT-Lym TOI

End point description

The median time, in month, from date of randomization until a clinically meaningful decline from baseline in TOI or death, whichever occurred first. TOI: sum of physical well-being score,functional well-being score, and Lymphoma sub-scale of FACT-Lym; total 29 items, responses to each item range from 0, “Not at all” to 4, “Very much”. Total score ranges from 0-116. Higher scores indicate a better PRO/QoL. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from baseline. Time to deterioration was estimated using Kaplan-Meier method and 95% CI for median was computed using the method of Brookmeyer and Crowley. In timeframe, follow-up months represents months after end of induction (EOI) (e.g. Follow-up Month 2 is 2 months after end of induction) and extension follow-up months represents months after end of 2 years normal follow-up (e.g. extension follow-up Month 6 is 6 months after end of normal 2 year follow-up).

End point type

Secondary

End point timeframe

Baseline up to approximately 4 years (Baseline, Day 1 of Cycles 1, 3, 4, 5, EOI treatment [up to Month 6]; Follow-up Months 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, Final Follow-up [up to 2 years after EOI]; Extension follow-up Months 6 and 18)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: Months
median (confidence interval 95%)	5.6 (3.9 to 7.0)	8.0 (5.9 to 14.7)

No statistical analyses for this end point

Secondary: Percentage of Participants With Definitive Improvement (DI) from Baseline in FACT-Lym Instrument Scores

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End point title

Percentage of Participants With Definitive Improvement (DI) from Baseline in FACT-Lym Instrument Scores

End point description

FACT-Lym: 42-items in 5 subscales. Responses to each item range from 0 (Not at all) to 4 (Very much). FACT-Lym Lymphoma subscale includes 15 items (total score range = 0-60). FACT-Lym TOI is sum of 3 subscales (physical well-being, functional well-being, lymphoma subscale) and includes 29 items (total score range = 0−116). FACT-Lym total score is sum of 42 items (total score ranges from 0−168). For all above, higher scores indicate a better PRO/QoL. DI from baseline: at least 3 point increase from baseline in FACT-Lym Lymphoma subscale; at least 6 point increase from baseline in FACT Lym TOI; at least 7 point increase from baseline in FACT Lym total scores. In timeframe, follow-up months represents months after EOI (e.g. Follow-up Month 2 is 2 months after EOI; EOI = up to Month 6).

End point type

Secondary

End point timeframe

Baseline, Cycle 5 Day 1 (C5D1) (Cycle length = 28 days), Follow-up Months 6 (FUM6), 12 (FUM12), 18 (FUM18), 24 (FUM24), Extension Follow Up Month 6 (Ext FUM6)

End point values	Bendamustine alone	Obinutuzumab + Bendamustine
Number of subjects analysed	209	204
Units: Percentage of participants
number (not applicable)
C5D1 (n=155, n=156) (>=3 pt increase)	30.3	41.7
FUM6 (n=87, n=119) (>=3 pt increase)	37.9	47.1
FUM12 (n=60, n=99) (>=3 pt increase)	36.7	46.5
FUM18 (n=45, n=83) (>=3 pt increase)	35.6	53.0
FUM24 (n=34, n=74) (>=3 pt increase)	35.3	50
Ext FUM6 (n=25, n=64) (>=3 pt increase)	36.0	57.8
C5D1 (n=156, n=157) (>=6 pt increase)	23.1	34.4
FUM6 (n=88, n=119) (>=6 pt increase)	29.5	43.7
FUM12 (n=61, n=100) (>=6 pt increase)	26.2	47.0
FUM18 (n=45, n=83) (>=6 pt increase)	28.9	51.8
FUM24 (n=34, n=74) (>=6 pt increase)	26.5	48.0
Ext FUM6 (n=25, n=64) (>=6 pt increase)	44	56.9
C5D1 (n=156, n=157) (>=7 pt increase)	24.4	28.0
FUM6 (n=88, n=119) (>=7 pt increase)	34.1	40.3
FUM12 (n=61, n=100) (>=7 pt increase)	31.1	45.0
FUM18 (n=45, n=83) (>=7 pt increase)	31.1	43.4
FUM24 (n=34, n=75) (>=7 pt increase)	20.6	42.7
Ext FUM6 (n=25, n=65) (>=7 pt increase)	32	47.7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 8.5 years

Adverse event reporting additional description

Safety population included all participants who received any amount of obinutuzumab or bendamustine therapy.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Bendamustine alone

Reporting group description

Participants received Bendamustine 120 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Reporting group title

Obinutuzumab + Bendamustine

Reporting group description

Serious adverse events	Bendamustine alone	Obinutuzumab + Bendamustine
Total subjects affected by serious adverse events
subjects affected / exposed	76 / 203 (37.44%)	91 / 204 (44.61%)
number of deaths (all causes)	100	84
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA
subjects affected / exposed	2 / 203 (0.99%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	2 / 2	1 / 1
deaths causally related to treatment / all	2 / 2	1 / 1
ADENOCARCINOMA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
ADENOCARCINOMA GASTRIC
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
BASAL CELL CARCINOMA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
BLADDER CANCER
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
BREAST CANCER
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
BRONCHIAL NEOPLASM
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
CHOLANGIOCARCINOMA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
COLORECTAL CANCER
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
INTESTINAL ADENOCARCINOMA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
LEIOMYOSARCOMA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
LEUKAEMIA
subjects affected / exposed	2 / 203 (0.99%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
LUNG NEOPLASM MALIGNANT
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
MALIGNANT MELANOMA
subjects affected / exposed	1 / 203 (0.49%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
MYELODYSPLASTIC SYNDROME
subjects affected / exposed	1 / 203 (0.49%)	3 / 204 (1.47%)
occurrences causally related to treatment / all	1 / 1	3 / 3
deaths causally related to treatment / all	0 / 0	1 / 1
POLYCYTHAEMIA VERA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
RENAL CANCER
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
SQUAMOUS CELL CARCINOMA
subjects affected / exposed	3 / 203 (1.48%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
T-CELL LYMPHOMA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
THYROID NEOPLASM
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
CIRCULATORY COLLAPSE
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
DEEP VEIN THROMBOSIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
HYPOTENSION
subjects affected / exposed	2 / 203 (0.99%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
CATHETER SITE PAIN
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
CHEST PAIN
subjects affected / exposed	2 / 203 (0.99%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
FATIGUE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
GENERAL PHYSICAL HEALTH DETERIORATION
subjects affected / exposed	0 / 203 (0.00%)	3 / 204 (1.47%)
occurrences causally related to treatment / all	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
HYPERTHERMIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
INFLUENZA LIKE ILLNESS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
MALAISE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	3 / 203 (1.48%)	6 / 204 (2.94%)
occurrences causally related to treatment / all	1 / 3	2 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
GRAFT VERSUS HOST DISEASE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Social circumstances
SOCIAL PROBLEM
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
CHYLOTHORAX
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
EMPHYSEMA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PLEURAL EFFUSION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PNEUMONIA ASPIRATION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PNEUMOTHORAX
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	3 / 203 (1.48%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
ANXIETY
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
MANIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
BLOOD CREATININE INCREASED
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
BORRELIA TEST
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
FEMUR FRACTURE
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
HEAD INJURY
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
HIP FRACTURE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
INFUSION RELATED REACTION
subjects affected / exposed	3 / 203 (1.48%)	7 / 204 (3.43%)
occurrences causally related to treatment / all	3 / 3	7 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
JAW FRACTURE
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
POST PROCEDURAL BILE LEAK
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
SEROMA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
STAB WOUND
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
VASCULAR PSEUDOANEURYSM
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
WRIST FRACTURE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
HYDROCELE
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	1 / 203 (0.49%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	2 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
ATRIAL FLUTTER
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
CARDIAC FAILURE
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
CORONARY ARTERY DISEASE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
MYOCARDIAL INFARCTION
subjects affected / exposed	1 / 203 (0.49%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
PAROXYSMAL ARRHYTHMIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
AMYOTROPHIC LATERAL SCLEROSIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
CENTRAL NERVOUS SYSTEM LESION
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
HEADACHE
subjects affected / exposed	1 / 203 (0.49%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ISCHAEMIC STROKE
subjects affected / exposed	2 / 203 (0.99%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
POST HERPETIC NEURALGIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PRESYNCOPE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
SUBARACHNOID HAEMORRHAGE
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
SYNCOPE
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
AGRANULOCYTOSIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
ANAEMIA
subjects affected / exposed	3 / 203 (1.48%)	3 / 204 (1.47%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	6 / 203 (2.96%)	11 / 204 (5.39%)
occurrences causally related to treatment / all	6 / 6	16 / 17
deaths causally related to treatment / all	0 / 0	0 / 0
LEUKOPENIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	1 / 203 (0.49%)	6 / 204 (2.94%)
occurrences causally related to treatment / all	1 / 1	5 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
THROMBOCYTOPENIA
subjects affected / exposed	0 / 203 (0.00%)	5 / 204 (2.45%)
occurrences causally related to treatment / all	0 / 0	5 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
NECROTISING RETINITIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
ANAL FISSURE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
COLITIS
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	3 / 203 (1.48%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
FOOD POISONING
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
HAEMATOCHEZIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
INTESTINAL PERFORATION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
LARGE INTESTINAL OBSTRUCTION
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
MELAENA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PANCREATITIS
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
RECTAL HAEMORRHAGE
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
VOMITING
subjects affected / exposed	1 / 203 (0.49%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
CHOLECYSTITIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
PARANEOPLASTIC PEMPHIGUS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
DYSURIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
END STAGE RENAL DISEASE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
HAEMATURIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
POLLAKIURIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
URETERIC OBSTRUCTION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
URINARY INCONTINENCE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
MUSCLE HAEMORRHAGE
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
OSTEOARTHRITIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
ATYPICAL PNEUMONIA
subjects affected / exposed	1 / 203 (0.49%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
BACTERAEMIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
BRONCHITIS
subjects affected / exposed	3 / 203 (1.48%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	1 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
CAMPYLOBACTER INFECTION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
COXSACKIE MYOCARDITIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
DEVICE RELATED SEPSIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
ENCEPHALITIS VIRAL
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ENDOCARDITIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
ERYSIPELAS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ESCHERICHIA SEPSIS
subjects affected / exposed	0 / 203 (0.00%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
FUNGAL SEPSIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
GASTROENTERITIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
GASTROENTERITIS NOROVIRUS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
HEPATITIS B REACTIVATION
subjects affected / exposed	1 / 203 (0.49%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
HERPES ZOSTER
subjects affected / exposed	3 / 203 (1.48%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	3 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
INFECTION
subjects affected / exposed	2 / 203 (0.99%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 203 (0.49%)	3 / 204 (1.47%)
occurrences causally related to treatment / all	0 / 5	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
LUNG INFECTION
subjects affected / exposed	1 / 203 (0.49%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
LUNG INFECTION PSEUDOMONAL
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
NEUTROPENIC SEPSIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
PNEUMOCYSTIS JIROVECII PNEUMONIA
subjects affected / exposed	2 / 203 (0.99%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	2 / 2	0 / 0
PNEUMONIA
subjects affected / exposed	12 / 203 (5.91%)	7 / 204 (3.43%)
occurrences causally related to treatment / all	6 / 12	2 / 7
deaths causally related to treatment / all	0 / 1	0 / 0
PNEUMONIA CYTOMEGALOVIRAL
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PSEUDOMONAL SEPSIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
PSEUDOMONAS BRONCHITIS
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
RESPIRATORY SYNCYTIAL VIRUS INFECTION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	7 / 203 (3.45%)	6 / 204 (2.94%)
occurrences causally related to treatment / all	4 / 7	3 / 6
deaths causally related to treatment / all	1 / 3	0 / 1
SEPTIC SHOCK
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
SINUSITIS
subjects affected / exposed	1 / 203 (0.49%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
STAPHYLOCOCCAL SEPSIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
TOOTH INFECTION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 203 (0.49%)	2 / 204 (0.98%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 203 (0.00%)	3 / 204 (1.47%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
UROSEPSIS
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
VASCULAR DEVICE INFECTION
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	2 / 203 (0.99%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
HYPERGLYCAEMIA
subjects affected / exposed	0 / 203 (0.00%)	1 / 204 (0.49%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	1 / 203 (0.49%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
TUMOUR LYSIS SYNDROME
subjects affected / exposed	2 / 203 (0.99%)	0 / 204 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Bendamustine alone	Obinutuzumab + Bendamustine
Total subjects affected by non serious adverse events
subjects affected / exposed	194 / 203 (95.57%)	200 / 204 (98.04%)
Vascular disorders
HYPOTENSION
subjects affected / exposed	1 / 203 (0.49%)	23 / 204 (11.27%)
occurrences all number	2	26
PHLEBITIS
subjects affected / exposed	13 / 203 (6.40%)	11 / 204 (5.39%)
occurrences all number	14	11
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	25 / 203 (12.32%)	31 / 204 (15.20%)
occurrences all number	35	44
CHEST PAIN
subjects affected / exposed	4 / 203 (1.97%)	11 / 204 (5.39%)
occurrences all number	4	11
CHILLS
subjects affected / exposed	21 / 203 (10.34%)	28 / 204 (13.73%)
occurrences all number	24	30
FATIGUE
subjects affected / exposed	67 / 203 (33.00%)	81 / 204 (39.71%)
occurrences all number	114	151
INFLUENZA LIKE ILLNESS
subjects affected / exposed	9 / 203 (4.43%)	11 / 204 (5.39%)
occurrences all number	10	12
MUCOSAL INFLAMMATION
subjects affected / exposed	8 / 203 (3.94%)	11 / 204 (5.39%)
occurrences all number	11	12
OEDEMA PERIPHERAL
subjects affected / exposed	14 / 203 (6.90%)	15 / 204 (7.35%)
occurrences all number	17	16
PYREXIA
subjects affected / exposed	36 / 203 (17.73%)	54 / 204 (26.47%)
occurrences all number	44	80
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	40 / 203 (19.70%)	64 / 204 (31.37%)
occurrences all number	46	85
DYSPNOEA
subjects affected / exposed	23 / 203 (11.33%)	26 / 204 (12.75%)
occurrences all number	28	27
NASAL CONGESTION
subjects affected / exposed	5 / 203 (2.46%)	17 / 204 (8.33%)
occurrences all number	6	18
OROPHARYNGEAL PAIN
subjects affected / exposed	7 / 203 (3.45%)	12 / 204 (5.88%)
occurrences all number	7	15
RHINORRHOEA
subjects affected / exposed	3 / 203 (1.48%)	11 / 204 (5.39%)
occurrences all number	3	11
Psychiatric disorders
INSOMNIA
subjects affected / exposed	21 / 203 (10.34%)	21 / 204 (10.29%)
occurrences all number	26	24
Investigations
WEIGHT DECREASED
subjects affected / exposed	18 / 203 (8.87%)	11 / 204 (5.39%)
occurrences all number	18	11
Injury, poisoning and procedural complications
INFUSION RELATED REACTION
subjects affected / exposed	115 / 203 (56.65%)	125 / 204 (61.27%)
occurrences all number	242	283
Nervous system disorders
DIZZINESS
subjects affected / exposed	17 / 203 (8.37%)	14 / 204 (6.86%)
occurrences all number	23	22
DYSGEUSIA
subjects affected / exposed	16 / 203 (7.88%)	15 / 204 (7.35%)
occurrences all number	20	20
HEADACHE
subjects affected / exposed	32 / 203 (15.76%)	27 / 204 (13.24%)
occurrences all number	37	36
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	34 / 203 (16.75%)	23 / 204 (11.27%)
occurrences all number	41	36
NEUTROPENIA
subjects affected / exposed	59 / 203 (29.06%)	74 / 204 (36.27%)
occurrences all number	103	150
THROMBOCYTOPENIA
subjects affected / exposed	50 / 203 (24.63%)	26 / 204 (12.75%)
occurrences all number	101	54
Gastrointestinal disorders
ABDOMINAL DISTENSION
subjects affected / exposed	11 / 203 (5.42%)	6 / 204 (2.94%)
occurrences all number	12	6
ABDOMINAL PAIN
subjects affected / exposed	20 / 203 (9.85%)	16 / 204 (7.84%)
occurrences all number	23	18
ABDOMINAL PAIN UPPER
subjects affected / exposed	15 / 203 (7.39%)	11 / 204 (5.39%)
occurrences all number	19	12
CONSTIPATION
subjects affected / exposed	40 / 203 (19.70%)	42 / 204 (20.59%)
occurrences all number	55	56
DIARRHOEA
subjects affected / exposed	61 / 203 (30.05%)	57 / 204 (27.94%)
occurrences all number	83	81
DRY MOUTH
subjects affected / exposed	12 / 203 (5.91%)	8 / 204 (3.92%)
occurrences all number	15	8
DYSPEPSIA
subjects affected / exposed	9 / 203 (4.43%)	13 / 204 (6.37%)
occurrences all number	11	16
NAUSEA
subjects affected / exposed	123 / 203 (60.59%)	107 / 204 (52.45%)
occurrences all number	227	210
VOMITING
subjects affected / exposed	54 / 203 (26.60%)	44 / 204 (21.57%)
occurrences all number	87	67
Skin and subcutaneous tissue disorders
PRURITUS
subjects affected / exposed	12 / 203 (5.91%)	29 / 204 (14.22%)
occurrences all number	13	38
RASH
subjects affected / exposed	24 / 203 (11.82%)	28 / 204 (13.73%)
occurrences all number	27	35
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	11 / 203 (5.42%)	24 / 204 (11.76%)
occurrences all number	12	31
BACK PAIN
subjects affected / exposed	18 / 203 (8.87%)	17 / 204 (8.33%)
occurrences all number	22	19
MYALGIA
subjects affected / exposed	15 / 203 (7.39%)	13 / 204 (6.37%)
occurrences all number	17	14
PAIN IN EXTREMITY
subjects affected / exposed	10 / 203 (4.93%)	22 / 204 (10.78%)
occurrences all number	13	27
Infections and infestations
BRONCHITIS
subjects affected / exposed	18 / 203 (8.87%)	24 / 204 (11.76%)
occurrences all number	23	36
HERPES ZOSTER
subjects affected / exposed	14 / 203 (6.90%)	10 / 204 (4.90%)
occurrences all number	16	10
NASOPHARYNGITIS
subjects affected / exposed	8 / 203 (3.94%)	22 / 204 (10.78%)
occurrences all number	10	27
RHINITIS
subjects affected / exposed	8 / 203 (3.94%)	12 / 204 (5.88%)
occurrences all number	9	13
SINUSITIS
subjects affected / exposed	11 / 203 (5.42%)	24 / 204 (11.76%)
occurrences all number	14	35
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	17 / 203 (8.37%)	26 / 204 (12.75%)
occurrences all number	21	34
URINARY TRACT INFECTION
subjects affected / exposed	12 / 203 (5.91%)	23 / 204 (11.27%)
occurrences all number	14	36
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	37 / 203 (18.23%)	37 / 204 (18.14%)
occurrences all number	49	40
HYPOKALAEMIA
subjects affected / exposed	15 / 203 (7.39%)	15 / 204 (7.35%)
occurrences all number	21	22

More information

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Were there any global substantial amendments to the protocol? Yes

11 Dec 2009

The protocol was amended to address feedback from the FDA during the Type B (pre Phase III) meeting held on 03 November 2009. The protocol was amended to modify bendamustine control arm dosing regimen from 90 mg/m^2 to 120 mg/m^2 which was given on Days 1 and 2 of a 28-day cycle, definition of rituximab-refractoriness was more clearly defined in the inclusion criteria. Eligibility criteria was also modified in order to allow more sites and countries to participate in the study.

28 Jul 2010

The protocol was amended to address feedback from the investigators and others since the first version of the protocol was issued. The exclusion criteria was modified to exclude participants who had received bendamustine; definition of rituximab-refractory iNHL was clarified; exclusion criterion regarding contraception was expanded to include participants who received only bendamustine; an early interim analysis for futility was added to the protocol in response to a recommendation by the independent data monitoring committee (IDMC); analysis of the FACT-Lym questionnaire was modified to capture changes in the participant's health-related QoL based on minimally important differences.

07 Dec 2011

The protocol was amended to address general issues related to the conduct of the trial, as well as comments from the IDMC, Investigators and study management team. A number of changes were made to eligibility criteria and some parameters were clarified.

01 May 2012

The protocol was amended to address general issues related to the conduct of the trial. The eligibility criteria was modified to allow for the enrollment of participant's previously treated with a bendamustine-containing regimen to reflect clinical practice so that participant's who were previously bendamustine responders and failed a subsequent regimen containing either an alkylating agent or anthracycline were allowed to participate in the study.

27 Nov 2012

This was a country-specific amendment for France to exclude participant's with a history of progressive multifocal encephalopathy (PML). The section on risks associated with obinutuzumab therapy was also updated with information on PML diagnosis, evaluation and guidance on how to manage a potential PML case.

06 Mar 2013

The protocol was amended to include revised information about PML; changes were made to some of the efficacy text (PFS assessment, secondary outcome measures and pharmacodynamic assessment) to align the protocol efficacy sections with the statistical analysis plan; requirement of administration of obinutuzumab after bendamustine on days when both drugs are given was deleted, so that the order in which the drugs are given is left to the discretion of the sites.

24 Oct 2013

The protocol was amended to allow for an increase in the number of participants enrolled from 360 to 410 and to extend the period of AE reporting in the comparator arm; collection of safety data was made consistent over the same timeframe for both treatment arms to more accurately assess the overall benefit/risk profile of adding obinutuzumab to bendamustine; period of AEs reporting in the comparator arm was extended in response to a recommendation by the IDMC; appendix E was also modifid to match the original wording of the revised response criteria for malignant lymphoma and current clinical practice.

10 Mar 2014

The protocol was amended following the identification of a higher incidence of thrombocytopenia and hemorrhagic events in participants with chronic lymphocytic leukemia receiving obinutuzumab; guidelines on the management of participant's with thrombocytopenia (especially during the first cycle), and participants receiving anticoagulants or platelet inhibitors were also added.

07 May 2015

This protocol version is a country-specific amendment implemented in Canada and the Czech Republic. The protocol was amended to offer the choice to participant's in the control arm receiving bendamustine to cross-over to the combination treatment arm (obinutuzumab plus bendamustine).

23 Aug 2017

A specific section for non-serious Adverse Events of Special Interest (AESIs) was added to align with reporting rules for other obinutuzumab/Gazyva/Gazyvaro protocols. The study was amended to consider second malignancies as an AESI and to report these events indefinitely, regardless of relationship to study treatment. The reporting requirements were amended to collect full information about the extent of events of second malignancies in real time. The protocol was modified to prohibit use of the term "sudden death" on the Adverse Event electronic Case Report Form (eCRF), unless it is combined with the presumed cause of death (e.g., "sudden cardiac death"). The Medical Monitor was changed and the contact information was revised. Language was modified to clarify the reporting requirements of all protocol-defined adverse events of special interest. The Roche study number (GO01297) was added to the protocol.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An Open-Label, Multicenter, Randomized, Phase III Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine + RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin’s Lymphoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death

Primary: Number of Participants With Progressive Disease (PD) as Assessed by Independent Review Committee (IRC) or Death

Primary: Progression-Free Survival (PFS) as Assessed by IRC

Primary: Progression-Free Survival (PFS) as Assessed by IRC

Secondary: Number of Participants With PD or Death as Assessed by Investigator

Secondary: Number of Participants With PD or Death as Assessed by Investigator

Secondary: PFS as Assessed by Investigator

Secondary: PFS as Assessed by Investigator

Secondary: Percentage of Participants With Objective Response as Assessed by IRC

Secondary: Percentage of Participants With Objective Response as Assessed by IRC

Secondary: Percentage of Participants With Objective Response as Assessed by Investigator

Secondary: Percentage of Participants With Objective Response as Assessed by Investigator

Secondary: Percentage of Participants with Best Overall Response (BOR) as Assessed by IRC

Secondary: Percentage of Participants with Best Overall Response (BOR) as Assessed by IRC

Secondary: Percentage of Participants with Best Overall Response (BOR) as Assessed by Investigator

Secondary: Percentage of Participants with Best Overall Response (BOR) as Assessed by Investigator

Secondary: Percentage of Participants with BOR at the End of induction Treatment as Assessed by IRC

Secondary: Percentage of Participants with BOR at the End of induction Treatment as Assessed by IRC

Secondary: Percentage of Participants with BOR at the End of induction Treatment as Assessed by Investigator

Secondary: Percentage of Participants with BOR at the End of induction Treatment as Assessed by Investigator

Secondary: Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC

Secondary: Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC

Secondary: Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator

Secondary: Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator

Secondary: Duration of Response (DoR) as Assessed by IRC

Secondary: Duration of Response (DoR) as Assessed by IRC

Secondary: Duration of Response (DoR) as Assessed by Investigator

Secondary: Duration of Response (DoR) as Assessed by Investigator

Secondary: Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC

Secondary: Disease-Free Survival (DFS) in Participants With CR as Assessed by IRC

Secondary: Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator

Secondary: Disease-Free Survival (DFS) in Participants With CR as Assessed by Investigator

Secondary: Event-free Survival (EFS) as Assessed by IRC

Secondary: Event-free Survival (EFS) as Assessed by IRC

Secondary: Percentage of Participants Who Died

Secondary: Percentage of Participants Who Died

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score

Secondary: Change From Baseline (CFB) in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)-Physical Well Being Sub-scale Score

Secondary: CFB in FACT-Lym-Social/Family Well-being Sub-scale Score

Secondary: CFB in FACT-Lym-Social/Family Well-being Sub-scale Score

Secondary: CFB in FACT-Lym-Emotional Well-Being Sub-scale Score

Secondary: CFB in FACT-Lym-Emotional Well-Being Sub-scale Score

Secondary: CFB in FACT-Lym-Functional Well-Being Sub-scale Score

Secondary: CFB in FACT-Lym-Functional Well-Being Sub-scale Score

Secondary: CFB in FACT-Lym-Lymphoma Sub-scale Score

Secondary: CFB in FACT-Lym-Lymphoma Sub-scale Score

Secondary: CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase

Secondary: CFB in Euro Quality of Life 5 Dimension (EuroQoL-5D/EQ-5D) - Health State Profile Utility Score During Induction Phase

Secondary: CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase

Secondary: CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase

Secondary: CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase

Secondary: CFB in EQ-5D Visual Analogue Scale (VAS) Score During Induction Phase

Secondary: CFB in EQ-5D VAS Score During Maintenance Phase

Secondary: CFB in EQ-5D VAS Score During Maintenance Phase

Secondary: CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score

Secondary: CFB in Functional Assessment of Cancer Therapy - Generic (FACT-G) Score

Secondary: CFB in FACT-Lym Trial Outcome Index (TOI)

Secondary: CFB in FACT-Lym Trial Outcome Index (TOI)

Secondary: CFB in FACT-Lym Total Score

Secondary: CFB in FACT-Lym Total Score

Secondary: Time to Deterioration of FACT-Lym TOI

Secondary: Time to Deterioration of FACT-Lym TOI

Secondary: Percentage of Participants With Definitive Improvement (DI) from Baseline in FACT-Lym Instrument Scores

Secondary: Percentage of Participants With Definitive Improvement (DI) from Baseline in FACT-Lym Instrument Scores

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
An Open-Label, Multicenter, Randomized, Phase III Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine + RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin’s Lymphoma