GAUSS: A Study of Obinutuzumab (RO5072759) in Patients With Indolent Non-Hodgkin's Lymphoma

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00576758
• Collaborator: (none)
• Enrollment: 175
• Locations: 71
• Arms: 2
• Duration (Months): 62
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will investigate the efficacy of weekly intravenous obinutuzumab [GA101 (RO5072759)] monotherapy, in patients with relapsed CD20+ indolent Non-Hodgkin's Lymphoma. Patients will be randomized to receive either GA101 or rituximab, given as four weekly infusions. At the conclusion of the initial trial patients may be eligible to continue therapy up to 24 months. The anticipated time on study treatment is 3- 24 months, and the target sample size is 100-500 individuals.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: obinutuzumab (RO5072759); Drug: rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 175 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multi-center, Randomized Study to Evaluate the Efficacy on Tumor Response of GA101 (RO5072759) Monotherapy Versus Rituximab Monotherapy in Patients With Relapsed CD20+ Indolent Non-Hodgkin's Lymphoma
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Drug: obinutuzumab (RO5072759); 1000 mg obinutuzumab intravenous (IV) infusion once a week for 4 weeks.; Other Names: RO5072759 GA101 GAZYVA®
Active Comparator: Rituximab Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Drug: rituximab; 375 mg/m^2 rituximab IV infusion once a week for 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Overall Response At the End of Induction Period [Randomization to clinical cutoff: 01 September 2011 (Up to 70 days)]

   Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigator at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Secondary Outcome Measures

1. Percentage of Participants With Complete Response at the End of the Induction Period [Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)]

   Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR is defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. All lymph nodes and nodal masses must have regressed to normal size. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Other organs considered to be enlarged before therapy due to involvement by lymphoma, such as liver and kidneys, must have decreased in size. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.

2. Percentage of Participants With Partial Response (PR) at the End of the Induction Period [Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)]

   Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

3. Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment [Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)]

   Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

4. Number of Participants With Improved Overall Response During the Extended Treatment Period [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

   Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.

5. Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

   Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

6. Progression-Free Survival (PFS) [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

   PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the Investigator. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

7. Percentage of Participants With Progression-Free Survival (PFS) Events [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

   The percentage of participants with progression, relapse, or death events from any cause as assessed by the Investigator. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

8. Event Free Survival [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

   Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

9. Percentage of Participants With Event Free Survival (EFS) Events [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

   Percentage of participants with Event Free Events: disease progression/relapse, death, or start of a new anti-leukemic therapy. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

10. Duration of Response [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

    Duration of Response was defined as the date the response, either Complete Response (CR) or Partial Response (PR), was first recorded until the date of Disease Progression or death due to any cause. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease. Disease Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

11. Obinutuzumab Serum PK Parameter: Terminal Half-Life (t1/2) [Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for Pharmacokinetic (PK) Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Terminal Half-Life was calculated in days.

12. Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax) [Day 1 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours post-infusion), Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycles 1, 2, 3 and 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was calculated in micrograms/milliliter (μg/mL).

13. Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve (AUClast) [Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). AUClast was calculated in days* micrograms/milliliter (μg/mL)

14. Obinutuzumab Serum PK Parameter: Clearance at Steady-State (CLss) [Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLsst was calculated in milliliter/day (mL/day)

15. Obinutuzumab Serum PK Parameter: Volume of Distribution at Steady-State (Vss) [Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Vss was calculated in liters (L).

16. Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve Between Dosing Interval (AUCtau) [Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). AUCtau was calculated in days* micrograms/milliliter (μg/mL)

17. Obinutuzumab Trough Serum Concentration (Ctrough) [Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)]

    Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycles 2, 3 and 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Ctrough was calculated in micrograms/milliliter (μg/mL).

18. Number of Participants With Peripheral Blood B-Cell Depletion [Day 22]

    Blood was collected and sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry at the end of the induction period. B-cell depletion was defined as a CD19 result 5 % of the Baseline value after at least one dose of study drug was administered.

19. Number of Participants With Peripheral Blood B-Cell Recovery [End of last dose + 6 Months Follow-Up]

    Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell recovery was defined as the time point when the CD-19 values return to ≥ 50% of baseline levels. The number of participants with B-cell recovery from End of Induction (treatment) Phase to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) or Recovery without PD. PD required one of the following: 50 % increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50 % increase in the longest diameter of any previous site of lymphadenopathy, 50 % increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology.

20. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) [Includes all AEs reported 28 days after last dose and all Related SAEs regardless of time of last dose.]]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory result), symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. A SAE was any AE that was one of the following: fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product or considered a significant medical event by the investigator. Additional information about AEs can be found in the Adverse Event Section.

21. Number of Participants With Infusion Related Reactions [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

    Infusion Related Reactions were AEs that occurred during the infusion or within 24 hours of the infusion.

22. Number of Participants With Human Anti-Chimeric Antibodies (HACA) [Day 1]

    Blood was collected on Day 1 and was sent to a central laboratory for analysis of human anti-chimeric antibodies (anti-rituximab antibodies) using a validated enzyme-linked immunosorbent assay (ELISA). HACA samples were not collected for participants randomized to the rituximab arm.

23. Number of Participants With Human Anti-Human Antibodies (HAHA) [Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)]

    Blood was collected on Day 1 pre-infusion, during the safety follow-up for those patients who did not enter the Extension period and 6 months after the last infusion of the Extension Period if applicable. Blood was sent to a central laboratory and was tested for anti-obinutuzumab antibodies using a validated enzyme-linked immunosorbent assay (ELISA). HAHA samples were not collected for participants randomized to the rituximab arm.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• adult patients, >=18 years of age

• relapsed CD20+ indolent B-cell non-Hodgkin's lymphoma

• documented history of response of >/= 6 months duration from last rituximab-containing regimen

• clinical indication for treatment as determined by the investigator

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

Exclusion Criteria:

• prior use of any investigational monoclonal antibody within 6 months of study start

• prior use of any anti-cancer vaccine

• prior use of rituximab within 8 weeks of study entry

• radioimmunotherapy within 3 months prior to study entry

• Central Nervous System (CNS) lymphoma or evidence of transformation to high-grade or diffuse large B-cell lymphoma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los angeles	California	United States	90024
2		Denver	Colorado	United States	80220
3		Gainesville	Florida	United States	32610
4		Tampa	Florida	United States	33612
5		Augusta	Georgia	United States	30912
6		Cumberland	Maryland	United States	21502
7		Hackensack	New Jersey	United States	07601
8		New York	New York	United States	10065
9		Rochester	New York	United States	14642
10		Concord	North Carolina	United States	28025
11		Columbus	Ohio	United States	43219
12		Houston	Texas	United States	77030
13		Seattle	Washington	United States	98109
14		Buenos Aires		Argentina	1406
15		Buenos Aires		Argentina	C1221ADC
16		Buenos Aires		Argentina	C1431FWO
17		Innsbruck		Austria	6020
18		Salzburg		Austria	5020
19		Wien		Austria	1090
20		Bruxelles		Belgium	1200
21		Gent		Belgium	9000
22		Mont-godinne		Belgium	5530
23		Goiania	GO	Brazil	74140-050
24		Porto Alegre	RS	Brazil	90035-903
25		Piracicaba	SP	Brazil	13419-155
26		Sao Paulo	SP	Brazil	01323-020
27		Sao Paulo	SP	Brazil	04029-000
28		Calgary	Alberta	Canada	T2N 4N2
29		Vancouver	British Columbia	Canada	V5Z 4E6
30		Kingston	Ontario	Canada	K7L 5P9
31		Toronto	Ontario	Canada	M4N 3M5
32		Toronto	Ontario	Canada	M5G 2M9
33		Montreal	Quebec	Canada	H3A 1A1
34		Montreal	Quebec	Canada	H3T 1E2
35		Rijeka		Croatia	51000
36		Zagreb		Croatia	10000
37		København		Denmark	2100
38		Vejle		Denmark	7100
39		Århus		Denmark	8000
40		Athens		Greece	115 27
41		Thessaloniki		Greece	570 10
42		Bologna		Italy	40138
43		Brescia		Italy	25123
44		Milano		Italy	20141
45		Milano		Italy	20162
46		Novara		Italy	28100
47		Pisa		Italy	56100
48		Reggio Calabria		Italy	89100
49		Rozzano		Italy	20089
50		Amsterdam		Netherlands	1105 AZ
51		Groningen		Netherlands	9713 GZ
52		Rotterdam		Netherlands	3015 CE
53		Rotterdam		Netherlands	3075EA
54		Warszawa		Poland	02-097
55		Warszawa		Poland	02-781
56		Palma de Mallorca	Islas Baleares	Spain	07198
57		La Coruna	La Coruña	Spain	15006
58		Barcelona		Spain	08025
59		Barcelona		Spain	08035
60		Madrid		Spain	28046
61		Salamanca		Spain	37007
62		Sevilla		Spain	41013
63		Valencia		Spain	46010
64		Zaragoza		Spain	50009
65		Huddinge		Sweden	14186
66		Malmo		Sweden	205 02
67		St. Gallen		Switzerland	9007
68		Zürich		Switzerland	8091
69		Istanbul		Turkey	34365
70		Izmir		Turkey	35100
71		London		United Kingdom	N6A 4L6

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00576758
• Other Study ID Numbers: BO21003
• First Posted: Dec 19, 2007
• Last Update Posted: Aug 19, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab; Obinutuzumab

Study Results

Participant Flow

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Period Title: Induction Treatment Period
STARTED	87	88
Received Treatment	86	87
COMPLETED	79	83
NOT COMPLETED	8	5
Period Title: Induction Treatment Period
STARTED	72	73
COMPLETED	30	30
NOT COMPLETED	42	43
Period Title: Induction Treatment Period
STARTED	55	51
COMPLETED	28	34
NOT COMPLETED	27	17

Baseline Characteristics

Arm/Group Title	Rituximab	Obinutuzumab	Total
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Total of all reporting groups
Overall Participants	87	88	175
Age, Customized (participants) [Number]
<65 years	49 56.3%	47 53.4%	96 54.9%
65-70 years	22 25.3%	22 25%	44 25.1%
>70 years	16 18.4%	19 21.6%	35 20%
Sex: Female, Male (Count of Participants)
Female	43 49.4%	42 47.7%	85 48.6%
Male	44 50.6%	46 52.3%	90 51.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Overall Response At the End of Induction Period
Description	Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigator at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.
Time Frame	Randomization to clinical cutoff: 01 September 2011 (Up to 70 days)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Number [Percentage of participants]	33.3 38.3%	44.6 50.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab, Obinutuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1587
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.26
	Confidence Interval	(2-Sided) 60%; 3.9 to 18.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Complete Response at the End of the Induction Period
Description	Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR is defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. All lymph nodes and nodal masses must have regressed to normal size. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Other organs considered to be enlarged before therapy due to involvement by lymphoma, such as liver and kidneys, must have decreased in size. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
Time Frame	Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Number (95% Confidence Interval) [Percentage of participants]	5.3 6.1%	12.2 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab, Obinutuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.83
	Confidence Interval	(2-Sided) 95%; -2.9 to 16.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Partial Response (PR) at the End of the Induction Period
Description	Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.
Time Frame	Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Number (95% Confidence Interval) [Percentage of participants]	28.0 32.2%	32.4 36.8%

4. Secondary Outcome

Title	Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment
Description	Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.
Time Frame	Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Complete Response	18.7 21.5%	35.1 39.9%
Partial Response	45.3 52.1%	31.1 35.3%
Stable Disease	26.7 30.7%	21.6 24.5%
Progressive Disease	5.3 6.1%	8.1 9.2%

5. Secondary Outcome

Title	Number of Participants With Improved Overall Response During the Extended Treatment Period
Description	Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis who received treatment in the extension period.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	63	62
Number [Participants]	31 35.6%	32 36.4%

6. Secondary Outcome

Title	Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment
Description	Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Complete Response	22.7 26.1%	41.9 47.6%
Partial Response	41.3 47.5%	24.3 27.6%
Stable Disease	26.7 30.7%	21.6 24.5%
Progressive Disease	5.3 6.1%	8.1 9.2%
No Response Assessment	4.0 4.6%	4.1 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab, Obinutuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.22
	Confidence Interval	(2-Sided) 95%; -13.9 to 18.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the Investigator. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with follicular non-Hodgkin's lymphoma at the time of diagnosis. If no PFS even occurred, PFS was censored at the date of the last tumor assessment. If no tumor assessment was available patient was censored at the date of the first study drug administration.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Median (95% Confidence Interval) [Days]	772	536

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab, Obinutuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Progression-Free Survival (PFS) Events
Description	The percentage of participants with progression, relapse, or death events from any cause as assessed by the Investigator. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Participants from the ITT population (all randomized participants) with follicular non-Hodgkin's lymphoma at the time of diagnosis. If event did not occur, PFS was censored at the date of the last tumor assessment. If no tumor assessment is available patient was censored at the date of the first study drug administration.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Number [Percentage of participants]	57.7 66.3%	51.4 58.4%

9. Secondary Outcome

Title	Event Free Survival
Description	Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with follicular non-Hodgkin's lymphoma at the time of diagnosis. If no EFS event occurred, EFS was censored at the date of the last tumor assessment. If no tumor assessment is available patient was censored at the date of the first study drug administration.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Median (95% Confidence Interval) [Days]	472.0	472.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab, Obinutuzumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Event Free Survival (EFS) Events
Description	Percentage of participants with Event Free Events: disease progression/relapse, death, or start of a new anti-leukemic therapy. Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy. Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Participants from the Intent-to-treat (ITT) population (all randomized participants) with follicular non-Hodgkin's lymphoma (NHL) at the time of diagnosis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	75	74
Number [Percentage of participants]	64.0 73.6%	63.5 72.2%

11. Secondary Outcome

Title	Duration of Response
Description	Duration of Response was defined as the date the response, either Complete Response (CR) or Partial Response (PR), was first recorded until the date of Disease Progression or death due to any cause. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease. Disease Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Participants from the ITT population (all randomized participants with follicular NHL at the time of diagnosis N=75/74] with response. Patients with no documented progression after CR or PR will be censored at the last tumor assessment. If no assessment available patients will be censored at the first study drug.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	48	49
Median (95% Confidence Interval) [Months]	809	NA

12. Secondary Outcome

Title	Obinutuzumab Serum PK Parameter: Terminal Half-Life (t1/2)
Description	Blood was collected for Pharmacokinetic (PK) Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Terminal Half-Life was calculated in days.
Time Frame	Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	72
Mean (Standard Deviation) [days]	41.0 (28.6)

13. Secondary Outcome

Title	Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax)
Description	Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycles 1, 2, 3 and 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was calculated in micrograms/milliliter (μg/mL).
Time Frame	Day 1 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours post-infusion), Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	78
Cycle 1 (n=74)	292 (87.4)
Cycle 2 (n=78)	448 (129)
Cycle 3 (n=77)	561 (158)
Cycle 4 (n=77)	692 (213)

14. Secondary Outcome

Title	Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve (AUClast)
Description	Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). AUClast was calculated in days* micrograms/milliliter (μg/mL)
Time Frame	Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	77
Mean (Standard Deviation) [day*μg/mL]	23400 (10300)

15. Secondary Outcome

Title	Obinutuzumab Serum PK Parameter: Clearance at Steady-State (CLss)
Description	Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLsst was calculated in milliliter/day (mL/day)
Time Frame	Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	72
Mean (Standard Deviation) [mL/day]	308 (470)

16. Secondary Outcome

Title	Obinutuzumab Serum PK Parameter: Volume of Distribution at Steady-State (Vss)
Description	Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Vss was calculated in liters (L).
Time Frame	Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	72
Mean (Standard Deviation) [Liter]	14.6 (9.8)

17. Secondary Outcome

Title	Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve Between Dosing Interval (AUCtau)
Description	Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycle 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). AUCtau was calculated in days* micrograms/milliliter (μg/mL)
Time Frame	Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	77
Mean (Standard Deviation) [day*μg/mL]	4370 (1340)

18. Secondary Outcome

Title	Obinutuzumab Trough Serum Concentration (Ctrough)
Description	Blood was collected for PK Parameters before and after dose administration of obinutuzumab in Induction Phase Cycles 2, 3 and 4. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Ctrough was calculated in micrograms/milliliter (μg/mL).
Time Frame	Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)

Outcome Measure Data

Analysis Population Description

PK Analysis Population included all participants who received obinutuzumab and had PK samples collected as per protocol. Patients with limited PK sampling time-points were excluded from the analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	78
Cycle 2 (n=78)	154 (62.7)
Cycle 3 (n=77)	301 (119)
Cycle 4 (n=75)	418 (147)

19. Secondary Outcome

Title	Number of Participants With Peripheral Blood B-Cell Depletion
Description	Blood was collected and sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry at the end of the induction period. B-cell depletion was defined as a CD19 result 5 % of the Baseline value after at least one dose of study drug was administered.
Time Frame	Day 22

Outcome Measure Data

Analysis Population Description

Participants from the Safety Population, all randomized participants who received study drug, with data available for analysis.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	84	85
Number [Participants]	80 92%	82 93.2%

20. Secondary Outcome

Title	Number of Participants With Peripheral Blood B-Cell Recovery
Description	Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell recovery was defined as the time point when the CD-19 values return to ≥ 50% of baseline levels. The number of participants with B-cell recovery from End of Induction (treatment) Phase to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) or Recovery without PD. PD required one of the following: 50 % increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50 % increase in the longest diameter of any previous site of lymphadenopathy, 50 % increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology.
Time Frame	End of last dose + 6 Months Follow-Up

Outcome Measure Data

Analysis Population Description

Participants from the Safety Population, all randomized participants who received study drug, with previous B-Cell Depletion and B-Cell assessment at 6 Month Follow-up.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	69	73
Recovery with PD	0 0%	2 2.3%
Recovery without PD	1 1.1%	0 0%

21. Secondary Outcome

Title	Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory result), symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. A SAE was any AE that was one of the following: fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product or considered a significant medical event by the investigator. Additional information about AEs can be found in the Adverse Event Section.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) [Includes all AEs reported 28 days after last dose and all Related SAEs regardless of time of last dose.]

Outcome Measure Data

Analysis Population Description

Safety Population included all randomized participants who received study drug.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	86	87
AE	74 85.1%	83 94.3%
SAE	17 19.5%	21 23.9%

22. Secondary Outcome

Title	Number of Participants With Infusion Related Reactions
Description	Infusion Related Reactions were AEs that occurred during the infusion or within 24 hours of the infusion.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all randomized participants who received at least once dose of study drug.

Arm/Group Title	Rituximab	Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	86	87
Number [Participants]	44 50.6%	70 79.5%

23. Secondary Outcome

Title	Number of Participants With Human Anti-Chimeric Antibodies (HACA)
Description	Blood was collected on Day 1 and was sent to a central laboratory for analysis of human anti-chimeric antibodies (anti-rituximab antibodies) using a validated enzyme-linked immunosorbent assay (ELISA). HACA samples were not collected for participants randomized to the rituximab arm.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Participants from the Safety Population, all randomized participants who received study drug, who had samples available for HACA analysis.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	86
Number [Participants]	1 1.1%

24. Secondary Outcome

Title	Number of Participants With Human Anti-Human Antibodies (HAHA)
Description	Blood was collected on Day 1 pre-infusion, during the safety follow-up for those patients who did not enter the Extension period and 6 months after the last infusion of the Extension Period if applicable. Blood was sent to a central laboratory and was tested for anti-obinutuzumab antibodies using a validated enzyme-linked immunosorbent assay (ELISA). HAHA samples were not collected for participants randomized to the rituximab arm.
Time Frame	Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all randomized participants who received study drug.

Arm/Group Title	Obinutuzumab
Arm/Group Description	Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Measure Participants	86
Number [Participants]	0 0%

Adverse Events

Time Frame	First dose of study drug to 28 days past last dose of study drug (Up to 27 Months)
Adverse Event Reporting Description	Safety population included all randomized patients who received at least one dose of study drug. Serious Adverse Events that occurred during treatment are reported.
Arm/Group Title	Rituximab		Obinutuzumab
Arm/Group Description	Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.		Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
All Cause Mortality
	Rituximab		Obinutuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab		Obinutuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/86 (15.1%)		13/87 (14.9%)
Blood and lymphatic system disorders
Febrile neutropenia	2/86 (2.3%)		2/87 (2.3%)
Eosinophilia	0/86 (0%)		1/87 (1.1%)
Neutropenia	1/86 (1.2%)		0/87 (0%)
Cardiac disorders
Angina pectoris	0/86 (0%)		1/87 (1.1%)
Cardio-respiratory arrest	1/86 (1.2%)		0/87 (0%)
Diastolic dysfunction	0/86 (0%)		1/87 (1.1%)
General disorders
Pyrexia	0/86 (0%)		1/87 (1.1%)
Hepatobiliary disorders
Hepatitis cholestatic	1/86 (1.2%)		0/87 (0%)
Infections and infestations
Pneumonia	2/86 (2.3%)		2/87 (2.3%)
Cellulitis	1/86 (1.2%)		0/87 (0%)
Herpes zoster disseminated	0/86 (0%)		1/87 (1.1%)
Chronic sinusitis	0/86 (0%)		1/87 (1.1%)
Respiratory tract infection	1/86 (1.2%)		0/87 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	1/86 (1.2%)		2/87 (2.3%)
Fibula fracture	1/86 (1.2%)		0/87 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer	1/86 (1.2%)		0/87 (0%)
Psychiatric disorders
Confusional state	1/86 (1.2%)		0/87 (0%)
Renal and urinary disorders
Renal colic	0/86 (0%)		1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	0/86 (0%)		1/87 (1.1%)
Cough	0/86 (0%)		1/87 (1.1%)
Dyspnoea	1/86 (1.2%)		0/87 (0%)
Pleural effusion	0/86 (0%)		1/87 (1.1%)
Other (Not Including Serious) Adverse Events
	Rituximab		Obinutuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/86 (81.4%)		79/87 (90.8%)
Blood and lymphatic system disorders
Neutropenia	6/86 (7%)		3/87 (3.4%)
Gastrointestinal disorders
Abdominal pain upper	6/86 (7%)		2/87 (2.3%)
Diarrhoea	7/86 (8.1%)		7/87 (8%)
Nausea	7/86 (8.1%)		8/87 (9.2%)
Vomiting	3/86 (3.5%)		4/87 (4.6%)
General disorders
Asthenia	5/86 (5.8%)		6/87 (6.9%)
Fatigue	17/86 (19.8%)		23/87 (26.4%)
Oedema peripheral	4/86 (4.7%)		6/87 (6.9%)
Pyrexia	9/86 (10.5%)		5/87 (5.7%)
Infections and infestations
Bronchitis	3/86 (3.5%)		7/87 (8%)
Influenza	5/86 (5.8%)		3/87 (3.4%)
Nasopharyngitis	4/86 (4.7%)		6/87 (6.9%)
Sinusitis	4/86 (4.7%)		6/87 (6.9%)
Upper respiratory tract infection	9/86 (10.5%)		9/87 (10.3%)
Rhinitis	4/86 (4.7%)		4/87 (4.6%)
Herpes zoster	2/86 (2.3%)		4/87 (4.6%)
Injury, poisoning and procedural complications
Infusion related reactions	43/86 (50%)		62/87 (71.3%)
Metabolism and nutrition disorders
Decreased appetite	3/86 (3.5%)		8/87 (9.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/86 (9.3%)		4/87 (4.6%)
Back pain	3/86 (3.5%)		7/87 (8%)
Myalgia	2/86 (2.3%)		5/87 (5.7%)
Nervous system disorders
Dizziness	6/86 (7%)		4/87 (4.6%)
Headache	7/86 (8.1%)		8/87 (9.2%)
Paraesthesia	2/86 (2.3%)		5/87 (5.7%)
Psychiatric disorders
Insomnia	1/86 (1.2%)		4/87 (4.6%)
Respiratory, thoracic and mediastinal disorders
Cough	8/86 (9.3%)		20/87 (23%)
Oropharyngeal pain	5/86 (5.8%)		2/87 (2.3%)
Skin and subcutaneous tissue disorders
Rash	3/86 (3.5%)		6/87 (6.9%)
Vascular disorders
Hypertension	7/86 (8.1%)		2/87 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.