Download PDF

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

Results information
Results version number	v1
This version publication date	12 Oct 2016
First version publication date	12 Oct 2016
Other versions	v2

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

Collapse all Expand all

Trial information

Top of page

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

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

Scientific contact

Roche Trial Information Hotline, 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

Interim

Date of interim/final analysis

01 Sep 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 Sep 2014

Global end of trial reached?

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

This study was conducted in accordance with the United States Food and Drug Administration (USFDA) regulations, the International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice, and applicable local, state, and federal laws, as well as other applicable country laws.

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: 95

Country: Number of subjects enrolled

Czech Republic: 30

Country: Number of subjects enrolled

France: 78

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Italy: 16

Country: Number of subjects enrolled

Netherlands: 17

Country: Number of subjects enrolled

Russian Federation: 22

Country: Number of subjects enrolled

Spain: 8

Country: Number of subjects enrolled

Sweden: 13

Country: Number of subjects enrolled

Switzerland: 2

Country: Number of subjects enrolled

United Kingdom: 29

Country: Number of subjects enrolled

United States: 69

Worldwide total number of subjects

396

EEA total number of subjects

208

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)

220

From 65 to 84 years

172

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

A total of 469 participants were screened; out of which 73 participants did not meet the inclusion/exclusion criteria.

Period 1 title

Induction Period (6 Months)

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 milligrams per meter square (mg/m^2) Intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for up to six cycles.

Arm type

Experimental

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 complete response (CR), partial response (PR) or stable disease (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	202	194
Treated	198	194
Completed	129	156
Not completed	73	38
Consent withdrawn by subject	7	2
Physician decision	2	4
Adverse Event	30	15
Death	2	2
Progressive Disease	14	9
Randomized but not Treated	4	-
Unspecified	1	-
Induction ongoing	13	6

Period 2 title

Maintenance Period (up to 2 Years)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Obinutuzumab + Bendamustine

Arm description

Arm type

Experimental

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

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

Number of subjects in period 2 ^[1]	Obinutuzumab + Bendamustine
Started	143
Completed	35
Not completed	108
Maintenance ongoing	46
Consent withdrawn by subject	3
Physician decision	2
Death	2
Progressive Disease	44
Unspecified	3
Adverse Events	8

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Of all participants who completed induction, 13 participants did not start maintenance.

Baseline characteristics

Top of page

Reporting group title

Bendamustine Alone

Reporting group description

Participants received Bendamustine 120 milligrams per meter square (mg/m^2) Intravenous (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	202	194	396
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	61.9 ( 11.4 )	61.9 ( 11.3 )	-
Gender categorical
Units: Subjects
Female	84	84	168
Male	118	110	228

End points

Top of page

Reporting group title

Bendamustine Alone

Reporting group description

Participants received Bendamustine 120 milligrams per meter square (mg/m^2) Intravenous (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 title

Obinutuzumab + Bendamustine

Reporting group description

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

Top of page

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. Intent to treat (ITT) population included all participants who were randomized in the study.

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 analysis was planned for this endpoint.

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	202	194
Units: participants
number (not applicable)	104	71

No statistical analyses for this end point

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

Top of page

End point title

Progression-Free Survival (PFS) as Assessed by IRC

End point description

PFS: time from randomization to first occurrence of PD or death as assessed by IRC according to modified response criteria for iNHL (modified Cheson et al, 2007). PD: appearance of any new lesion more than 1.5 cm in any axis during or at end of therapy, even if other lesions decrease 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 (e.g., splenic or hepatic nodules). To be PD, lymph node with diameter of short axis of <1.0 cm must increase by ≥ 50% and to size of 1.5 multiplied by 1.5 cm or more than 1.5 cm in long axis; at least 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. ITT population. The number 99999 signified data could not be estimated 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	202	194
Units: months
median (confidence interval 95%)	14.9 (12.8 to 16.6)	99999 (22.5 to 99999)

Statistical Analysis 1

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

396

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0.74

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

Top of page

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. ITT population.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	202	194
Units: participants
number (not applicable)	115	77

No statistical analyses for this end point

Secondary: PFS as Assessed by Investigator

Top of page

End point title

PFS as Assessed by Investigator

End point description

PFS: time from randomization to first occurrence of PD as assessed by investigator according to modified response criteria for iNHL (Modified Cheson et al, 2007), or death from any cause on study. PD: appearance of any new lesion more than 1.5 cm in any axis during/at end of therapy, even if other lesions decreases 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. To be considered PD, lymph node with 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 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 method of Brookmeyer and Crowley. ITT population. The number 99999 signified data could not be estimated due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	202	194
Units: Months
median (confidence interval 95%)	14 (11.7 to 16)	29.2 (20.2 to 99999)

Statistical Analysis 1

Statistical analysis description

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

0.7

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

Top of page

End point title

Percentage of Participants With Objective Response as Assessed by IRC and Investigator

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. ITT population. Here, number of participants analyzed signified those participants who had at least one post-baseline assessment.

End point type

Secondary

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 12 months overall)

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	197	192
Units: percentage of participants
number (confidence interval 95%)
IRC Assessment	76.6 (70.11 to 82.37)	78.6 (72.17 to 84.22)
Investigator Assessment	82.2 (76.17 to 87.3)	82.8 (76.72 to 87.86)

Statistical Analysis 1

Statistical analysis description

Statistical Analysis 1 for Percentage of Participants With Objective Response as Assessed by IRC.

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

389

Analysis specification

Pre-specified

Analysis type

^[2]

P-value

= 0.743

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6.56

upper limit

10.55

Notes
[2] - Statistical analysis for IRC assessment.

Statistical Analysis 2

Statistical analysis description

Statistical Analysis 2 for Percentage of Participants With Objective Response as Assessed by Investigator.

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

389

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

= 0.8946

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-7.25

upper limit

8.41

Notes
[3] - [Not specified]

Secondary: Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC and Investigator

Top of page

End point title

Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC and 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 the other nodes, liver, or spleen; 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 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. ITT population. Here, number of participants analyzed signified those participants who had at least one post-baseline assessment.

End point type

Secondary

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 12 months overall)

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	197	192
Units: percentage of participants
number (confidence interval 95%)
IRC Assessment: CR	17.3 (12.26 to 23.27)	16.7 (11.69 to 22.71)
IRC Assessment: PR	59.4 (52.18 to 66.31)	62 (54.71 to 68.87)
IRC Assessment: SD	11.7 (7.55 to 17)	10.9 (6.9 to 16.23)
IRC Assessment: PD	4.1 (1.77 to 7.84)	4.7 (2.17 to 8.71)
IRC Assessment: Unable to evaluate	0.5 (0.01 to 2.8)	1 (0.13 to 3.71)
IRC Assessment: Missing	7.1 (3.94 to 11.64)	4.7 (2.17 to 8.71)
Investigator Assessment: CR	21.3 (15.82 to 27.71)	22.4 (16.71 to 28.96)
Investigator Assessment: PR	60.9 (53.72 to 67.77)	60.4 (53.12 to 67.38)
Investigator Assessment: SD	6.6 (3.56 to 11.02)	6.8 (3.65 to 11.3)
Investigator Assessment: PD	3.6 (1.44 to 7.18)	5.7 (2.89 to 10.02)
Investigator Assessment: Unable to evaluate	1.5 (0.32 to 4.39)	0.5 (0.01 to 2.87)
Investigator Assessment: Missing	6.1 (3.19 to 10.4)	4.2 (1.82 to 8.04)

No statistical analyses for this end point

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

Top of page

End point title

Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC and 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	189	188
Units: percentage of participants
number (confidence interval 95%)
IRC Assessment	63 (55.65 to 69.86)	69.1 (62.02 to 75.67)
Investigator Assessment	67.7 (60.56 to 74.33)	76.6 (69.88 to 82.45)

Statistical Analysis 1

Statistical analysis description

Statistical Analysis 1 for Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by IRC.

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[4]

P-value

= 0.3062

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

6.19

Confidence interval

level

95%

sides

2-sided

lower limit

-3.64

upper limit

16.02

Notes
[4] - [Not specified]

Statistical Analysis 2

Statistical analysis description

Statistical Analysis 2 for Percentage of Participants With Objective Response at the End of Induction Treatment as Assessed by Investigator.

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

377

Analysis specification

Pre-specified

Analysis type

^[5]

P-value

= 0.0506

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

8.87

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

18.16

Notes
[5] - [Not specified]

Secondary: Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC and Investigator

Top of page

End point title

Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC and 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	189	188
Units: percentage of participants
number (confidence interval 95%)
IRC Assessment: CR	12.2 (7.87 to 17.7)	11.2 (7.05 to 16.57)
IRC Assessment: PR	50.8 (43.44 to 58.12)	58 (50.58 to 65.12)
IRC Assessment: SD	9.5 (5.74 to 14.63)	10.1 (6.2 to 15.33)
IRC Assessment: PD	9 (5.33 to 14.01)	9 (5.36 to 14.08)
IRC Assessment: Unable to Evaluate	2.6 (0.86 to 6.07)	2.1 (0.58 to 5.36)
IRC Assessment: Missing	15.9 (10.97 to 21.88)	9.6 (5.77 to 14.71)
Investigator Assessment: CR	15.9 (10.97 to 21.88)	16.5 (11.49 to 22.58)
Investigator Assessment: PR	51.9 (44.48 to 59.16)	60.1 (52.73 to 67.16)
Investigator Assessment: SD	3.2 (1.17 to 6.78)	4.3 (1.85 to 8.21)
Investigator Assessment: PD	11.1 (7.01 to 16.48)	9 (5.36 to 14.08)
Investigator Assessment: Unable to Evaluate	3.2 (1.17 to 6.78)	0.5 (0.01 to 2.93)
Investigator Assessment: Missing	14.8 (10.08 to 20.69)	9.6 (5.77 to 14.71)

No statistical analyses for this end point

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

Top of page

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 clinical evidence of disease and disease-related symptoms if present prior to therapy; liver, spleen returned to normal size (if enlarged at baseline); if bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. 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

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	154	154
Units: months
median (confidence interval 95%)	13.2 (11 to 14.1)	99999 (25.4 to 99999)

Statistical Analysis 1

Statistical analysis description

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

^[6]

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

0.61

Notes
[6] - [Not specified]

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

Top of page

End point title

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

End point description

DFS: time from first occurrence of 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, liver and spleen returned to normal size if enlarged at baseline, If bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PD: appearance of any new lesion >1.5 cm in any axis during/at end of therapy, even if other lesions decreases 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. DFS was estimated using Kaplan-Meier method. ITT population. Number of participants analyzed signified participants who had an objective response of CR. Number 99999 signified data could not be estimated due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	35	42
Units: months
median (confidence interval 95%)	13.2 (8.2 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Statistical analysis description

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

^[7]

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.02

upper limit

0.4

Notes
[7] - [Not specified]

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

Top of page

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. ITT population. The number 99999 signified data could not be estimated due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	202	194
Units: months
median (confidence interval 95%)	13.7 (11.4 to 16.2)	26.8 (14.1 to 99999)

Statistical Analysis 1

Statistical analysis description

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

^[8]

P-value

= 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

0.76

Notes
[8] - [Not specified

Secondary: Percentage of Participants Who Died

Top of page

End point title

Percentage of Participants Who Died

End point description

ITT population.

End point type

Secondary

End point timeframe

Baseline until death (up to 4.5 years overall)

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	202	194
Units: percentage of participants
number (not applicable)	20.3	17.5

No statistical analyses for this end point

Secondary: Overall Survival (OS)

Top of page

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. ITT population. The number 99999 signified data could not be estimated due to higher (>50%) number of censored participants.

End point type

Secondary

End point timeframe

Baseline until death (up to 4.5 years overall)

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	202	194
Units: months
median (confidence interval 95%)	99999 (39.8 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Statistical analysis description

Comparison groups

Bendamustine Alone v Obinutuzumab + Bendamustine

Number of subjects included in analysis

396

Analysis specification

Pre-specified

Analysis type

P-value

= 0.4017

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

1.3

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

Top of page

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

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 range: 0-168. Physical well-being sub-scale includes 7 items measured on 0-4 point scale; total score ranges from 0-28. Higher scores indicates 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); 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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available either because no participant or only one participant was evaluable.

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 and 18

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	181	177
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=181, 177)	22.63 ( 5.16 )	22.72 ( 4.65 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=146, 147)	-1.78 ( 5.47 )	-0.77 ( 4.13 )
CFB at Cycle 4 Day 1 (n=5, 2)	-6.8 ( 4.21 )	-3 ( 2.83 )
CFB at Cycle 5 Day 1 (n=130, 137)	-1.99 ( 5.07 )	-0.77 ( 4.22 )
CFB at End of Induction Treatment (n= 132, 135)	-0.96 ( 5.23 )	-0.63 ( 4.71 )
CFB at Follow-up Month 2 (n=91, 119)	0.42 ( 5.21 )	0.57 ( 4.46 )
CFB at Follow-up Month 4 (n= 80, 108)	0.36 ( 4.44 )	0.84 ( 4.32 )
CFB at Follow-up Month 6 (n= 67, 94)	0.31 ( 3.74 )	0.77 ( 3.62 )
CFB at Follow-up Month 8 (n= 62, 86)	-0.12 ( 3.42 )	0.78 ( 3.82 )
CFB at Follow-up Month 10 (n= 47, 71)	-0.28 ( 4.42 )	0.47 ( 4.01 )
CFB at Follow-up Month 12 (n= 38, 70)	0.5 ( 4.26 )	0.66 ( 4.6 )
CFB at Follow-up Month 14 (n= 32, 62)	0.14 ( 4.24 )	0.5 ( 4 )
CFB at Follow-up Month 16 (n= 26, 59)	-0.47 ( 3.36 )	0.86 ( 3.62 )
CFB at Follow-up Month 18 (n= 23, 50)	-0.22 ( 4.03 )	0.6 ( 4.27 )
CFB at Follow-up Month 20 (n= 22, 41)	-0.31 ( 3.96 )	0.35 ( 4.23 )
CFB at Follow-up Month 22 (n=16, 38)	-0.73 ( 4.06 )	-0.15 ( 5.32 )
CFB at Follow-up Month 24 (n=15, 33)	-1.23 ( 3.81 )	0.35 ( 5.42 )
CFB at Final Follow-up (n=59, 58)	-0.09 ( 4.15 )	0.12 ( 5.17 )
CFB at Extension Follow-up Month 6 (n= 7, 18)	0.31 ( 2.6 )	1.09 ( 5.33 )
CFB at Extension Follow-up Month 18 (n= 1, 1)	1 ( 99999 )	7 ( 99999 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

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 range: 0-168. Social/family well-being sub-scale includes 7 items measured on 0-4 point scale; total score ranges from 0-28. Higher scores indicates 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); 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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	180	181
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=180, 181)	22.14 ( 5.58 )	22.17 ( 5.48 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=145, 151)	-0.35 ( 3.39 )	-0.1 ( 3.94 )
CFB at Cycle 4 Day 1 (n=5, 3)	-1 ( 3.67 )	3.11 ( 2.83 )
CFB at Cycle 5 Day 1 (n=129, 141)	-0.82 ( 3.45 )	-0.39 ( 4.4 )
CFB at End of Induction Treatment (n=131, 138)	-1.06 ( 4.69 )	-0.91 ( 3.62 )
CFB at Follow-up Month 2 (n=90, 123)	-0.48 ( 3.89 )	-0.59 ( 5.54 )
CFB at Follow-up Month 4 (n=80, 111)	0.09 ( 3.76 )	-0.26 ( 5.2 )
CFB at Follow-up Month 6 (n=67, 95)	-0.14 ( 2.84 )	-0.07 ( 4.81 )
CFB at Follow-up Month 8 (n=62, 88)	-0.48 ( 3.48 )	-0.47 ( 5.19 )
CFB at Follow-up Month 10 (n=47, 73)	0.05 ( 3.45 )	0.16 ( 5.38 )
CFB at Follow-up Month 12 (n=38, 72)	0.13 ( 2.31 )	-0.14 ( 5.53 )
CFB at Follow-up Month 14 (n=32, 64)	0.82 ( 3.32 )	-0.17 ( 3.86 )
CFB at Follow-up Month 16 (n=26, 61)	0.41 ( 3.68 )	0.4 ( 5.63 )
CFB at Follow-up Month 18 (n=23, 51)	0.3 ( 3.89 )	0.49 ( 6.02 )
CFB at Follow-up Month 20 (n=22, 43)	-0.82 ( 4.61 )	0.82 ( 6.14 )
CFB at Follow-up Month 22 (n=16, 40)	-0.97 ( 5.47 )	-0.39 ( 5.41 )
CFB at Follow-up Month 24 (n=15, 34)	-0.97 ( 2.56 )	0.23 ( 4.32 )
CFB at Final Follow-up (n=59, 59)	-0.47 ( 3.34 )	-0.3 ( 5.36 )
CFB at Extension Follow-up Month 6 (n=7, 18)	-0.64 ( 2.68 )	0.62 ( 4.01 )
CFB at Extension Follow-up Month 18 (n=1, 1)	-1 ( 99999 )	10 ( 99999 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

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 range: 0-168. Emotional well-being sub-scale includes 6 items measured on 0-4 point scale; total score ranges from 0-24. Higher scores indicates 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); 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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	183	184
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=183, 184)	17.43 ( 4.44 )	17.73 ( 4.33 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=147, 156)	0.54 ( 3.07 )	0.75 ( 3.14 )
CFB at Cycle 4 Day 1 (n=5, 3)	-0.6 ( 3.85 )	3.4 ( 4.42 )
CFB at Cycle 5 Day 1 (n=131, 144)	0.32 ( 3.11 )	0.5 ( 3.59 )
CFB at End of Induction Treatment (n=133, 138)	0.53 ( 3.59 )	0.48 ( 3.97 )
CFB at Follow-up Month 2 (n=90, 124)	0.74 ( 4.03 )	0.58 ( 3.67 )
CFB at Follow-up Month 4 (n=81, 110)	1.37 ( 3.5 )	0.88 ( 3.41 )
CFB at Follow-up Month 6 (n=68, 97)	0.94 ( 3.42 )	0.97 ( 3.29 )
CFB at Follow-up Month 8 (n=62, 89)	0.29 ( 3.55 )	0.76 ( 3.23 )
CFB at Follow-up Month 10 (n=46, 73)	0.72 ( 3.59 )	1.17 ( 2.95 )
CFB at Follow-up Month 12 (n=38, 72)	-0.08 ( 3.98 )	0.84 ( 3.01 )
CFB at Follow-up Month 14 (n=32, 64)	0.43 ( 3.48 )	0.93 ( 3.58 )
CFB at Follow-up Month 16 (n=26, 62)	0.08 ( 3.77 )	0.95 ( 3.49 )
CFB at Follow-up Month 18 (n=22, 52)	0.41 ( 3.1 )	0.92 ( 3.01 )
CFB at Follow-up Month 20 (n=22, 44)	-0.14 ( 2.82 )	0.84 ( 4.45 )
CFB at Follow-up Month 22 (n=16, 40)	-0.38 ( 2.7 )	0.88 ( 3.84 )
CFB at Follow-up Month 24 (n=15, 35)	-0.2 ( 3.19 )	0.95 ( 3.76 )
CFB at Final Follow-up (n=58, 61)	0.03 ( 3.85 )	0.1 ( 4.9 )
CFB at Extension Follow-up Month 6 (n=7, 18)	-0.43 ( 5.09 )	1.21 ( 4.68 )
CFB at Extension Follow-up Month 18 (n=1, 1)	1 ( 99999 )	8 ( 99999 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

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 range: 0-168. Functional well-being sub-scale includes 7 items measured on 0-4 point scale; total score ranges from 0-28. Higher scores indicates 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); 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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	183	186
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=183, 186)	18 ( 6.18 )	17.84 ( 6.07 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=147, 158)	-0.64 ( 4.7 )	0.39 ( 4.74 )
CFB at Cycle 4 Day 1 (n=5, 3)	-0.8 ( 2.28 )	1.78 ( 4.91 )
CFB at Cycle 5 Day 1 (n=131, 146)	-0.88 ( 5.04 )	0.67 ( 5.48 )
CFB at End of Induction Treatment (n=133, 140)	-0.58 ( 5.68 )	0 ( 5.35 )
CFB at Follow-up Month 2 (n=90, 125)	0.32 ( 5.54 )	0.74 ( 5.48 )
CFB at Follow-up Month 4 (n=81, 112)	0.36 ( 5.14 )	1.3 ( 5.77 )
CFB at Follow-up Month 6 (n=67, 97)	0.81 ( 4.65 )	1.58 ( 5.05 )
CFB at Follow-up Month 8 (n=62, 89)	-0.21 ( 4.38 )	1.03 ( 5.75 )
CFB at Follow-up Month 10 (n=47, 74)	1 ( 4.42 )	1.23 ( 5.93 )
CFB at Follow-up Month 12 (n=38, 73)	1.11 ( 4.82 )	1.96 ( 6.63 )
CFB at Follow-up Month 14 (n=32, 64)	1.47 ( 4.53 )	1.39 ( 5.12 )
CFB at Follow-up Month 16 (n=26, 62)	0.89 ( 4.17 )	2.14 ( 6.14 )
CFB at Follow-up Month 18 (n=22, 52)	0.1 ( 4.98 )	1.87 ( 6.77 )
CFB at Follow-up Month 20 (n=22, 44)	-0.81 ( 4.55 )	1.52 ( 7.31 )
CFB at Follow-up Month 22 (n=16, 41)	-1.74 ( 4.9 )	0.71 ( 6.06 )
CFB at Follow-up Month 24 (n=15, 35)	-1.86 ( 4.46 )	1.5 ( 6.84 )
CFB at Final Follow-up (n=58, 63)	-1.03 ( 4.95 )	0.66 ( 7.17 )
CFB at Extension Follow-up Month 6 (n=7, 18)	1.45 ( 5.16 )	2.61 ( 7.46 )
CFB at Extension Follow-up Month 18 (n=1, 1)	-2 ( 99999 )	0 ( 99999 )

No statistical analyses for this end point

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

Top of page

End point title

CFB in FACT-Lym-Lymphoma Sub-scale Score

End point description

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 range: 0-168. Lymphoma sub-scale includes 15 items measured on 0-4 point scale; total score ranges from 0-60. Higher scores indicates 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); 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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	183	144
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=183, 144)	44.88 ( 9.56 )	45.55 ( 9.18 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=144, 155)	0.68 ( 6.95 )	1.05 ( 5.58 )
CFB at Cycle 4 Day 1 (n=5, 2)	-2.8 ( 5.76 )	9.5 ( 3.54 )
CFB at Cycle 5 Day 1 (n=130, 143)	0.88 ( 6.87 )	1.26 ( 6.1 )
CFB at End of Induction Treatment (n=131, 141)	1.88 ( 7.18 )	0.79 ( 7.99 )
CFB at Follow-up Month 2 (n=90, 121)	3.63 ( 6.86 )	2.48 ( 6.19 )
CFB at Follow-up Month 4 (n=81, 109)	2.7 ( 7.08 )	2.55 ( 6.3 )
CFB at Follow-up Month 6 (n=69, 97)	2.57 ( 6.65 )	3.45 ( 6.36 )
CFB at Follow-up Month 8 (n=61, 88)	1.63 ( 6.16 )	3.04 ( 6.34 )
CFB at Follow-up Month 10 (n=47, 72)	1.69 ( 7.1 )	2.61 ( 6.41 )
CFB at Follow-up Month 12 (n=38, 73)	2.53 ( 7.35 )	3.23 ( 6.5 )
CFB at Follow-up Month 14 (n=32, 65)	0.37 ( 7.27 )	3.09 ( 6.02 )
CFB at Follow-up Month 16 (n=25, 61)	0 ( 9.58 )	3.62 ( 6.5 )
CFB at Follow-up Month 18 (n=23, 51)	1.69 ( 7.33 )	3.07 ( 7.37 )
CFB at Follow-up Month 20 (n=21, 42)	1.33 ( 8.47 )	3.14 ( 7.4 )
CFB at Follow-up Month 22 (n=16, 38)	1.19 ( 8.24 )	3.17 ( 6.94 )
CFB at Follow-up Month 24 (n=15, 33)	0.4 ( 5.91 )	3.25 ( 6.97 )
CFB at Final Follow-up (n=58, 61)	1.27 ( 7.04 )	1.6 ( 7.73 )
CFB at Extension Follow-up Month 6 (n=7, 17)	1.29 ( 5.5 )	4.95 ( 8.23 )
CFB at Extension Follow-up Month 18 (n=1, 1)	-4 ( 99999 )	4 ( 99999 )

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

Top of page

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 which assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state; 3 indicates worst health state. Score is transformed, results in total score range -0.594 to 1.000; higher score indicates 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 follow-up Months 2 and 4 visits before start of maintenance treatment were reported in induction phase under “CFB at Follow-up Month 2” and “CFB at Follow-up Month 4” categories. ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome; “n” signified those participants who were evaluable for specified time point. Number 99999 signified data not available as no participant was evaluable.

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, and 4

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	180	185
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=180, 185)	0.77 ( 0.23 )	0.79 ( 0.2 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=147, 156)	0.03 ( 0.21 )	0 ( 0.2 )
CFB at Cycle 4 Day 1 (n=5, 3)	-0.1 ( 0.23 )	-0.07 ( 0.41 )
CFB at Cycle 5 Day 1 (n=130, 146)	0.01 ( 0.21 )	0.02 ( 0.22 )
CFB at End of Induction Treatment (n=123, 135)	0.03 ( 0.2 )	0 ( 0.22 )
CFB at Follow-up Month 2 (n=32, 122)	0.07 ( 0.26 )	0.03 ( 0.15 )
CFB at Follow-up Month 4 (n=0, 2)	99999 ( 99999 )	-0.12 ( 0 )

No statistical analyses for this end point

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

Top of page

End point title

CFB in EuroQol 5D (EQ-5D) - Health State Profile Utility Score During Maintenance Phase ^[9]

End point description

EQ-5D: participant rated questionnaire to assess health-related QoL in terms of single utility score. It assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state; 3 indicates worst health state. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates better health state. Data for this outcome was planned to be reported only for ‘Obinutuzumab + Bendamustine’ arm as ’Bendamustine Alone’ arm did not have maintenance phase treatment. 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. ITT population (Obinutuzumab + Bendamustine arm only). Here, number of participants analyzed signified those participants who were evaluable for this outcome;“n” signified those participants who were evaluable for a specified time point.

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)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was applicable for only "Obinutuzumab + Bendamustine" arm.

End point values	Obinutuzumab + Bendamustine
Number of subjects analysed	143
Units: units on a scale
arithmetic mean (standard deviation)
CFB at Follow-up Month 2 (n=2)	-0.15 ( 0.22 )
CFB at Follow-up Month 4 (n=106)	0.02 ( 0.19 )
CFB at Follow-up Month 6 (n=93)	0.02 ( 0.16 )
CFB at Follow-up Month 8 (n=82)	0.02 ( 0.17 )
CFB at Follow-up Month 10 (n=70)	0.03 ( 0.14 )
CFB at Follow-up Month 12 (n=66)	0.05 ( 0.14 )
CFB at Follow-up Month 14 (n=58)	0.04 ( 0.13 )
CFB at Follow-up Month 16 (n=56)	0.03 ( 0.14 )
CFB at Follow-up Month 18 (n=47)	0.03 ( 0.12 )
CFB at Follow-up Month 20 (n=40)	0.05 ( 0.13 )
CFB at Follow-up Month 22 (n=39)	0.04 ( 0.21 )
CFB at Follow-up Month 24 (n=33)	0.02 ( 0.21 )
CFB at Final Follow-up (n=21)	0.02 ( 0.13 )

No statistical analyses for this end point

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

Top of page

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. 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 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. ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available because no participant was evaluable for this time point.

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 and 4

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	178	178
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=178, 178)	-69.39 ( 20.61 )	68.03 ( 21.33 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=143, 146)	0.5 ( 19.26 )	3.48 ( 16.09 )
CFB at Cycle 4 Day 1 (n=5, 3)	-14 ( 33.29 )	-4.33 ( 42.15 )
CFB at Cycle 5 Day 1 (n=125, 133)	-0.29 ( 20.89 )	5.26 ( 17.66 )
CFB at End of Induction Treatment (n=119, 129)	6.75 ( 64.84 )	6.09 ( 22.48 )
CFB at Follow-up Month 2 (n=30, 114)	5.2 ( 20.48 )	7.43 ( 18.97 )
CFB at Follow-up Month 4 (n=0, 2)	99999 ( 99999 )	0 ( 14.14 )

No statistical analyses for this end point

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

Top of page

End point title

CFB in EQ-5D VAS Score During Maintenance Phase ^[10]

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. ITT population (Obinutuzumab + Bendamustine arm only). Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The number 99999 signified data not available as only one participant was evaluable for this time point.

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)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was applicable for only "Obinutuzumab + Bendamustine" arm.

End point values	Obinutuzumab + Bendamustine
Number of subjects analysed	143
Units: units on a scale
arithmetic mean (standard deviation)
CFB at Follow-up Month 2 (n=1)	-40 ( 99999 )
CFB at Follow-up Month 4 (n=98)	5.96 ( 19.8 )
CFB at Follow-up Month 6 (n=87)	7.21 ( 18.91 )
CFB at Follow-up Month 8 (n=76)	5.62 ( 16.78 )
CFB at Follow-up Month 10 (n=65)	6.08 ( 15.26 )
CFB at Follow-up Month 12 (n=62)	5.82 ( 16.57 )
CFB at Follow-up Month 14 (n=54)	6.76 ( 16.59 )
CFB at Follow-up Month 16 (n=53)	6.91 ( 18.37 )
CFB at Follow-up Month 18 (n=44)	4.5 ( 20.6 )
CFB at Follow-up Month 20 (n=38)	5.76 ( 16.48 )
CFB at Follow-up Month 22 (n=35)	6.14 ( 17.3 )
CFB at Follow-up Month 24 (n=30)	5.67 ( 18.71 )
CFB at Final Follow-up (n=20)	1.05 ( 9.48 )

No statistical analyses for this end point

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

Top of page

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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The Number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	179	177
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=179, 177)	80.07 ( 15.87 )	80.61 ( 16.19 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=144, 147)	-2.43 ( 12.28 )	-0.02 ( 10.49 )
CFB at Cycle 4 Day 1 (n=5, 2)	-9.37 ( 9.89 )	0.52 ( 4.98 )
CFB at Cycle 5 Day 1 (n=128, 137)	-3.28 ( 11.72 )	-0.04 ( 11.37 )
CFB at End of Induction Treatment (n=129, 133)	-2.23 ( 13.8 )	-1.08 ( 11.87 )
CFB at Follow-up Month 2 (n=90, 119)	0.96 ( 13.78 )	1.15 ( 12 )
CFB at Follow-up Month 4 (n=80, 107)	2.34 ( 11.13 )	2.84 ( 12.92 )
CFB at Follow-up Month 6 (n=65, 93)	2.28 ( 10.1 )	3.33 ( 11.52 )
CFB at Follow-up Month 8 (n=61, 86)	-0.54 ( 10.15 )	2.14 ( 11.73 )
CFB at Follow-up Month 10 (n=46, 68)	1.17 ( 11.14 )	3.44 ( 12.4 )
CFB at Follow-up Month 12 (n=38, 70)	1.63 ( 11.44 )	2.98 ( 15.28 )
CFB at Follow-up Month 14 (n=32, 61)	2.77 ( 9.85 )	2.44 ( 12.25 )
CFB at Follow-up Month 16 (n=26, 59)	0.8 ( 8.22 )	4.37 ( 13.4 )
CFB at Follow-up Month 18 (n=22, 50)	0.65 ( 12.12 )	3.99 ( 15.03 )
CFB at Follow-up Month 20 (n=22, 41)	-2.2 ( 12.18 )	2.98 ( 16.64 )
CFB at Follow-up Month 22 (n=16, 38)	-3.97 ( 12.71 )	0.86 ( 13.96 )
CFB at Follow-up Month 24 (n=15, 33)	-4.43 ( 8.13 )	2.57 ( 15.49 )
CFB at Final Follow-up (n=58, 58)	-1.47 ( 11.29 )	0.72 ( 17.13 )
CFB at Extension Follow Up Month 6 (n=7, 18)	0.52 ( 11.58 )	5.46 ( 15.99 )
CFB at Extension Follow Up Month 18 (n=1, 1)	-1 ( 99999 )	25 ( 99999 )

No statistical analyses for this end point

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

Top of page

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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. The Number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	184	186
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=184, 186)	84.79 ( 19.01 )	84.53 ( 19.03 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=149, 158)	-2.61 ( 18.09 )	1.6 ( 14.03 )
CFB at Cycle 4 Day 1 (n=5, 3)	-10.4 ( 10.38 )	26.44 ( 19.51 )
CFB at Cycle 5 Day 1 (n=132, 146)	-1.55 ( 15.6 )	2.23 ( 14.34 )
CFB at End of Induction Treatment (n=134, 142)	-0.4 ( 17.9 )	0.44 ( 16.73 )
CFB at Follow-up Month 2 (n=91, 125)	3.63 ( 15.93 )	4.81 ( 14.98 )
CFB at Follow-up Month 4 (n=81, 113)	3.75 ( 13.67 )	5.16 ( 17.03 )
CFB at Follow-up Month 6 (n=69, 97)	3.34 ( 12.36 )	6.56 ( 13.08 )
CFB at Follow-up Month 8 (n=62, 89)	0.68 ( 12.96 )	6.25 ( 14.09 )
CFB at Follow-up Month 10 (n=47, 74)	2.42 ( 13.99 )	5.3 ( 16.66 )
CFB at Follow-up Month 12 (n=38, 73)	4.14 ( 14.46 )	6.92 ( 16.37 )
CFB at Follow-up Month 14 (n=32, 65)	1.98 ( 12.49 )	5.82 ( 14.5 )
CFB at Follow-up Month 16 (n=26, 62)	-1.46 ( 15.97 )	6.93 ( 16.65 )
CFB at Follow-up Month 18 (n=23, 52)	0.69 ( 12.84 )	7.57 ( 16.55 )
CFB at Follow-up Month 20 (n=22, 44)	-2.03 ( 16.54 )	7.01 ( 18.23 )
CFB at Follow-up Month 22 (n=16, 41)	-1.28 ( 11.66 )	3.29 ( 23.02 )
CFB at Follow-up Month 24 (n=15, 35)	-2.69 ( 10.7 )	6.75 ( 21.25 )
CFB at Final Follow-up (n=59, 63)	-0.9 ( 15.31 )	4.8 ( 18.47 )
CFB at Extension Follow Up Month 6 (n=7, 18)	3.05 ( 11.34 )	5.6 ( 20.67 )
CFB at Extension Follow Up Month 18 (n=1, 1)	-5 ( 99999 )	11 ( 99999 )

No statistical analyses for this end point

Secondary: CFB in FACT-Lym Total Score

Top of page

End point title

CFB in FACT-Lym Total Score

End point description

FACT-Lym total score: 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 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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified time point. Number 99999 signified data not available either because no participant or only one participant was evaluable.

End point type

Secondary

End point timeframe

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	180	177
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=180, 177)	124.86 ( 23.63 )	126 ( 23.96 )
CFB at Cycle 1 Day 1 (n=0, 0)	99999 ( 99999 )	99999 ( 99999 )
CFB at Cycle 3 Day 1 (n=143, 147)	-1.61 ( 17.85 )	1 ( 13.96 )
CFB at Cycle 4 Day 1 (n=5, 2)	-12.16 ( 14.8 )	22.53 ( 16.23 )
CFB at Cycle 5 Day 1 (n=128, 136)	-2.37 ( 16.63 )	1.47 ( 15.44 )
CFB at End of Induction Treatment (n=130, 133)	-0.11 ( 18.91 )	0.25 ( 18.5 )
CFB at Follow-up Month 2 (89, 117)	4.74 ( 18.22 )	3.48 ( 15.18 )
CFB at Follow-up Month 4 (n=80, 105)	5.14 ( 16.39 )	5.57 ( 17.28 )
CFB at Follow-up Month 6 (n=66, 95)	5.08 ( 14.88 )	6.85 ( 15.59 )
CFB at Follow-up Month 8 (n=61, 86)	1.23 ( 14.48 )	5.46 ( 15.84 )
CFB at Follow-up Month 10 (n=47, 70)	3.2 ( 16.87 )	5.74 ( 17.58 )
CFB at Follow-up Month 12 (n= 38, 71)	4.19 ( 17.76 )	6.41 ( 20.02 )
CFB at Follow-up Month 14 (n= 32, 62)	3.13 ( 14.51 )	5.97 ( 17.35 )
CFB at Follow-up Month 16 (n=25, 59)	1.18 ( 14.22 )	8.49 ( 17.45 )
CFB at Follow-up Month 18 (n=22, 49)	2.11 ( 16.99 )	7.33 ( 20.14 )
CFB at Follow-up Month 20 (n=21, 40)	-0.92 ( 16.7 )	6.16 ( 21.85 )
CFB at Follow-up Month 22 (n=16, 37)	-2.66 ( 14.13 )	4.74 ( 20.21 )
CFB at Follow-up Month 24 (n=15, 32)	-3.98 ( 11.86 )	6.11 ( 21.48 )
CFB at Final follow-up (n=58, 56)	-0.18 ( 16.66 )	2.86 ( 22.89 )
CFB at Extension Follow Up Month 6 (n=7, 17)	1.8 ( 16.55 )	10.93 ( 22.57 )
CFB at Extension Follow Up Month 18 (n=1, 1)	-5 ( 99999 )	29 ( 99999 )

No statistical analyses for this end point

Secondary: Time to Deterioration of FACT-Lym TOI

Top of page

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 EOI) 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). ITT population.

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	202	194
Units: months
median (confidence interval 95%)	4.6 (3.8 to 6.4)	8 (5.8 to 15.1)

No statistical analyses for this end point

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

Top of page

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). ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and “n” signified those participants who were evaluable for a specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 5 Day 1 (C5D1) (Cycle length = 28 days), Follow-up Months 6 (FUM6), and 12 (FUM12)

End point values	Bendamustine Alone	Obinutuzumab + Bendamustine
Number of subjects analysed	184	186
Units: percentage of participants
number (not applicable)
DI in Lymphoma sub-scale: C5D1 (n=142, 148)	31	41.2
DI in Lymphoma sub-scale: FUM6 (n=76, 99)	38.2	48.5
DI in Lymphoma sub-scale: FUM12 (n=44, 77)	38.6	48.1
DI in FACT Lym TOI: C5D1 (n=143, 149)	22.4	34.9
DI in FACT Lym TOI: FUM6 (n=77, 99)	28.6	43.4
DI in FACT Lym TOI: FUM12 (n=44, 77)	27.3	48.1
DI in FACT Total: C5D1 (n=143, 149)	23.1	27.5
DI in FACT Total: FUM6 (n=77, 99)	33.8	42.4
DI in FACT Total: FUM12 (n=44, 77)	29.5	45.5

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to 4.5 years

Adverse event reporting additional description

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

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

Obinutuzumab + Bendamustine

Reporting group 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 received obinutuzumab 1000 mg IV infusion every 2 months until disease progression or for up to 2 years (whichever occurred first).

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.

Serious adverse events	Obinutuzumab + Bendamustine	Bendamustine Alone
Total subjects affected by serious adverse events
subjects affected / exposed	74 / 194 (38.14%)	65 / 198 (32.83%)
number of deaths (all causes)	42	56
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
subjects affected / exposed	1 / 194 (0.52%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	1 / 1	1 / 1
Adenocarcinoma
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Bladder cancer
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colorectal cancer
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Leiomyosarcoma
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leukaemia
subjects affected / exposed	0 / 194 (0.00%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
Malignant melanoma
subjects affected / exposed	1 / 194 (0.52%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	2 / 194 (1.03%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Paraneoplastic pemphigus
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Polycythaemia vera
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
T-cell lymphoma
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Thyroid neoplasm
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	2 / 194 (1.03%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 194 (0.00%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza like illness
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malaise
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	5 / 194 (2.58%)	3 / 198 (1.52%)
occurrences causally related to treatment / all	2 / 5	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Graft versus host disease
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Social circumstances
Social problem
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Social stay hospitalisation
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chylothorax
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Emphysema
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 194 (0.52%)	3 / 198 (1.52%)
occurrences causally related to treatment / all	1 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mania
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (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	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	6 / 194 (3.09%)	3 / 198 (1.52%)
occurrences causally related to treatment / all	6 / 6	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Jaw fracture
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural bile leak
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Seroma
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stab wound
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Wrist fracture
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (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	2 / 194 (1.03%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 194 (0.52%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Paroxysmal arrhythmia
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Central nervous system lesion
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 194 (0.52%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Presyncope
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Agranulocytosis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Anaemia
subjects affected / exposed	3 / 194 (1.55%)	3 / 198 (1.52%)
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	8 / 194 (4.12%)	6 / 198 (3.03%)
occurrences causally related to treatment / all	12 / 13	6 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	6 / 194 (3.09%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	5 / 6	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	4 / 194 (2.06%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Necrotising retinitis
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 194 (0.00%)	4 / 198 (2.02%)
occurrences causally related to treatment / all	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 194 (1.03%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pollakiuria
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure chronic
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Ureteric obstruction
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary incontinence
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Atypical pneumonia
subjects affected / exposed	1 / 194 (0.52%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 194 (0.00%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Fungal sepsis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis B
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	2 / 194 (1.03%)	3 / 198 (1.52%)
occurrences causally related to treatment / all	2 / 2	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 194 (0.00%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	3 / 194 (1.55%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	1 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
subjects affected / exposed	1 / 194 (0.52%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumocystis jirovecii pneumonia
subjects affected / exposed	1 / 194 (0.52%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	2 / 2
Pneumonia
subjects affected / exposed	5 / 194 (2.58%)	10 / 198 (5.05%)
occurrences causally related to treatment / all	2 / 5	6 / 10
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumonia cytomegaloviral
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Sepsis
subjects affected / exposed	6 / 194 (3.09%)	7 / 198 (3.54%)
occurrences causally related to treatment / all	3 / 6	4 / 7
deaths causally related to treatment / all	0 / 1	1 / 3
Sinusitis
subjects affected / exposed	2 / 194 (1.03%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth infection
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	2 / 194 (1.03%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	3 / 194 (1.55%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 194 (0.52%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	1 / 194 (0.52%)	0 / 198 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 194 (0.00%)	1 / 198 (0.51%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tumour lysis syndrome
subjects affected / exposed	0 / 194 (0.00%)	2 / 198 (1.01%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 1

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

Non-serious adverse events	Obinutuzumab + Bendamustine	Bendamustine Alone
Total subjects affected by non serious adverse events
subjects affected / exposed	187 / 194 (96.39%)	187 / 198 (94.44%)
Vascular disorders
Hypotension
subjects affected / exposed	22 / 194 (11.34%)	1 / 198 (0.51%)
occurrences all number	25	2
Phlebitis
subjects affected / exposed	11 / 194 (5.67%)	13 / 198 (6.57%)
occurrences all number	11	14
General disorders and administration site conditions
Asthenia
subjects affected / exposed	29 / 194 (14.95%)	23 / 198 (11.62%)
occurrences all number	40	32
Chest pain
subjects affected / exposed	10 / 194 (5.15%)	3 / 198 (1.52%)
occurrences all number	10	3
Chills
subjects affected / exposed	24 / 194 (12.37%)	20 / 198 (10.10%)
occurrences all number	26	23
Fatigue
subjects affected / exposed	76 / 194 (39.18%)	66 / 198 (33.33%)
occurrences all number	144	113
Oedema peripheral
subjects affected / exposed	12 / 194 (6.19%)	14 / 198 (7.07%)
occurrences all number	13	17
Pain
subjects affected / exposed	5 / 194 (2.58%)	10 / 198 (5.05%)
occurrences all number	6	10
Pyrexia
subjects affected / exposed	50 / 194 (25.77%)	33 / 198 (16.67%)
occurrences all number	74	40
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	54 / 194 (27.84%)	34 / 198 (17.17%)
occurrences all number	72	39
Dyspnoea
subjects affected / exposed	22 / 194 (11.34%)	21 / 198 (10.61%)
occurrences all number	23	26
Nasal congestion
subjects affected / exposed	16 / 194 (8.25%)	5 / 198 (2.53%)
occurrences all number	17	6
Oropharyngeal pain
subjects affected / exposed	11 / 194 (5.67%)	7 / 198 (3.54%)
occurrences all number	14	7
Rhinorrhoea
subjects affected / exposed	11 / 194 (5.67%)	3 / 198 (1.52%)
occurrences all number	11	3
Psychiatric disorders
Insomnia
subjects affected / exposed	21 / 194 (10.82%)	21 / 198 (10.61%)
occurrences all number	24	26
Investigations
Weight decreased
subjects affected / exposed	9 / 194 (4.64%)	17 / 198 (8.59%)
occurrences all number	9	17
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	123 / 194 (63.40%)	113 / 198 (57.07%)
occurrences all number	281	238
Nervous system disorders
Dizziness
subjects affected / exposed	13 / 194 (6.70%)	17 / 198 (8.59%)
occurrences all number	20	23
Dysgeusia
subjects affected / exposed	15 / 194 (7.73%)	16 / 198 (8.08%)
occurrences all number	20	20
Headache
subjects affected / exposed	26 / 194 (13.40%)	32 / 198 (16.16%)
occurrences all number	35	37
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	23 / 194 (11.86%)	28 / 198 (14.14%)
occurrences all number	36	34
Neutropenia
subjects affected / exposed	66 / 194 (34.02%)	56 / 198 (28.28%)
occurrences all number	126	92
Thrombocytopenia
subjects affected / exposed	26 / 194 (13.40%)	47 / 198 (23.74%)
occurrences all number	54	87
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	7 / 194 (3.61%)	11 / 198 (5.56%)
occurrences all number	7	12
Abdominal pain
subjects affected / exposed	12 / 194 (6.19%)	18 / 198 (9.09%)
occurrences all number	13	21
Abdominal pain upper
subjects affected / exposed	10 / 194 (5.15%)	15 / 198 (7.58%)
occurrences all number	11	19
Constipation
subjects affected / exposed	41 / 194 (21.13%)	38 / 198 (19.19%)
occurrences all number	54	53
Diarrhoea
subjects affected / exposed	53 / 194 (27.32%)	59 / 198 (29.80%)
occurrences all number	71	78
Dry mouth
subjects affected / exposed	8 / 194 (4.12%)	11 / 198 (5.56%)
occurrences all number	8	14
Dyspepsia
subjects affected / exposed	12 / 194 (6.19%)	8 / 198 (4.04%)
occurrences all number	15	10
Nausea
subjects affected / exposed	104 / 194 (53.61%)	121 / 198 (61.11%)
occurrences all number	204	220
Vomiting
subjects affected / exposed	42 / 194 (21.65%)	54 / 198 (27.27%)
occurrences all number	63	87
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	10 / 194 (5.15%)	4 / 198 (2.02%)
occurrences all number	11	4
Pruritus
subjects affected / exposed	25 / 194 (12.89%)	12 / 198 (6.06%)
occurrences all number	33	13
Rash
subjects affected / exposed	24 / 194 (12.37%)	23 / 198 (11.62%)
occurrences all number	30	26
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	23 / 194 (11.86%)	9 / 198 (4.55%)
occurrences all number	28	10
Back pain
subjects affected / exposed	13 / 194 (6.70%)	18 / 198 (9.09%)
occurrences all number	14	22
Myalgia
subjects affected / exposed	12 / 194 (6.19%)	15 / 198 (7.58%)
occurrences all number	13	17
Pain in extremity
subjects affected / exposed	18 / 194 (9.28%)	10 / 198 (5.05%)
occurrences all number	22	13
Infections and infestations
Bronchitis
subjects affected / exposed	18 / 194 (9.28%)	17 / 198 (8.59%)
occurrences all number	29	21
Herpes zoster
subjects affected / exposed	6 / 194 (3.09%)	13 / 198 (6.57%)
occurrences all number	6	15
Nasopharyngitis
subjects affected / exposed	17 / 194 (8.76%)	8 / 198 (4.04%)
occurrences all number	22	10
Sinusitis
subjects affected / exposed	22 / 194 (11.34%)	10 / 198 (5.05%)
occurrences all number	32	12
Upper respiratory tract infection
subjects affected / exposed	23 / 194 (11.86%)	15 / 198 (7.58%)
occurrences all number	28	18
Urinary tract infection
subjects affected / exposed	18 / 194 (9.28%)	11 / 198 (5.56%)
occurrences all number	29	13
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	34 / 194 (17.53%)	35 / 198 (17.68%)
occurrences all number	36	47
Hypokalaemia
subjects affected / exposed	14 / 194 (7.22%)	12 / 198 (6.06%)
occurrences all number	20	15

More information

Top of page

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).

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

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 and Investigator

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

Secondary: Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC and Investigator

Secondary: Percentage of Participants With Best Overall Response (BOR) as Assessed by IRC and Investigator

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

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

Secondary: Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC and Investigator

Secondary: Percentage of Participants With BOR at the End of Induction Treatment as Assessed by IRC and Investigator

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

Secondary: Duration of Response (DoR) 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 IRC

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)

Interruptions (globally)

Limitations and caveats

More information

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