Trial Outcomes & Findings for A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE) (NCT NCT01414205)

Last Updated: 2017-04-17

Results Overview

ORR was defined as the percentage of participants with complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR) as assessed by the investigator according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines two months after last treatment. CR required: blood lymphocytes \< 4 x 10\^9/Liter (L), absence of lymphadenopathy (≤ 1.5 centimeter (cm) in long axis by Computed Tomography), no hepatomegaly or splenomegaly, absence of disease, Neutrophils \> 1.5 x 10\^9/L, Platelets \> 100 x 10\^9/L, Hemoglobin \>11 g/dL, bone marrow normal and lymphoid nodules absent. CRi was CR with incomplete marrow recovery. PR required: 50% decrease in peripheral blood lymphocyte count, 50% reduction in lymphadenopathy, 50% reduction of liver and/or spleen enlargement if enlarged at baseline, Neutrophils \> 1.5 x 10\^9/L or \> 50% of pretreatment value, Platelets \> 100 x 10\^9/L or 50% of pretreatment value and Hemoglobin \> 11 g/dL or \> 50% of pretreatment value.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Week 32

Results posted on

2017-04-17

Participant Flow

Participant milestones

Participant milestones
Measure	Obinutuzumab 1000 mg Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Study STARTED	41	39
Overall Study Received Study Drug	40	38
Overall Study COMPLETED	34	32
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Obinutuzumab 1000 mg Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Study Death	5	1
Overall Study Lost to Follow-up	1	4
Overall Study Physician Decision	0	1
Overall Study Randomized but not Treated	1	1

Baseline Characteristics

A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Obinutuzumab 1000 mg n=41 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=39 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Total n=80 Participants Total of all reporting groups
Age, Continuous	67.0 years STANDARD_DEVIATION 10.0 • n=5 Participants	64.3 years STANDARD_DEVIATION 12.4 • n=7 Participants	65.7 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 32

Population: Intent-to-treat population included all randomized participants.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=41 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=39 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Objective Response Rate (ORR)	48.8 Percentage of participants	66.7 Percentage of participants

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Intent-to-treat population included all randomized participants.

PFS was defined as the time from the randomization to the first occurrence of progression or death, whichever occurred first.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=41 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=39 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Progression-free Survival (PFS)	25.2 Months Interval 15.9 to 30.4	26.0 Months Interval 20.2 to 34.2

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Duration of response was not analyzed as investigators did not perform response assessments at regular intervals during the follow-up period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Intent-to-treat population included all randomized participants.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=41 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=39 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Number of Participants Surviving at End-of-Study	35 Participants	37 Participants

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

An AE was defined as any unfavorable and unintended sign, 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.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=40 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Adverse Events	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Serious Adverse Events	20.0 Percentage of participants	21.1 Percentage of participants

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

Adverse Events of interest for this study were: serious infusion related reactions during or within 24 hours of infusion, serious neutropenia, serious infection, tumor lysis syndrome and Hepatitis B reactivation.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=40 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Percentage of Participants With Adverse Events of Interest Serious Infusion-Related Reactions (IRR)	7.5 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With Adverse Events of Interest Serious Neutropenia	5.0 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With Adverse Events of Interest Serious Infection	5.0 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With Adverse Events of Interest Tumor Lysis Syndrome	0.0 Percentage of participants	2.6 Percentage of participants
Percentage of Participants With Adverse Events of Interest Hepatitis B Reactivation	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=40 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Percentage of Participants With Adverse Events Leading to Study Discontinuation	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 148 (at end of infusion)

Population: All randomized participants who received study drug with PK data available for analysis.

Blood was collected for Pharmacokinetic (PK) Parameter Cmax after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=37 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=33 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
PK Parameter: Maximum Serum Concentration (Cmax)	600 μg/mL Geometric Coefficient of Variation 45.6	1190 μg/mL Geometric Coefficient of Variation 34.9

SECONDARY outcome

Timeframe: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

Population: All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.

Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in day times micrograms per milliliter (day\*μg/mL).

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=26 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=25 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt )	8230 day*μg/mL Geometric Coefficient of Variation 58.3	16500 day*μg/mL Geometric Coefficient of Variation 50.3

SECONDARY outcome

Timeframe: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

Population: All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.

Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLss is reported in milliliters per day (mL/day).

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=26 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=25 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
PK Parameter: Clearance at Steady State (CLss)	121 mL/day Geometric Coefficient of Variation 58.3	122 mL/day Geometric Coefficient of Variation 50.3

SECONDARY outcome

Timeframe: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

Population: All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=24 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=23 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
PK Parameter: Volume of Distribution at Steady State (Vss)	7.08 Liters Geometric Coefficient of Variation 73.2	6.68 Liters Geometric Coefficient of Variation 74.7

SECONDARY outcome

Timeframe: Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)

Population: All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=24 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=23 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
PK Parameter: Terminal Half-Life (t1/2)	30.6 Days Geometric Coefficient of Variation 87.1	26.3 Days Geometric Coefficient of Variation 80.1

SECONDARY outcome

Timeframe: Months 3, 6, 9, and 12

Population: All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.

Blood serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=37 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=33 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits) Month 3 (n=14, 10)	41.2 μg/mL Standard Deviation 63.3	98.9 μg/mL Standard Deviation 88.9
PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits) Month 6 (n=19, 15)	15 μg/mL Standard Deviation 21.4	12.6 μg/mL Standard Deviation 17.7
PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits) Month 9 (n=24, 23)	2.63 μg/mL Standard Deviation 4.4	4.09 μg/mL Standard Deviation 9.42
PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits) Month 12 (n=16, 18)	0.633 μg/mL Standard Deviation 1.11	0.857 μg/mL Standard Deviation 1.74

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Participants from the Safety Evaluable Population, all randomized participants who received at least one dose of study drug, who had data available for this outcome measure.

Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell depletion was defined as a CD19 result \< 0.07 × 10\^9/L after at least one dose of study drug has been administered.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=40 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Within 30-36 Months of Follow-up (n=1, 3)	1 Participants	3 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion At Last Antibody Administration (n=40, 38)	31 Participants	31 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Up to 6 Months of Follow-Up (FU) (n=30, 31)	28 Participants	28 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Within 6-12 Months of Follow-up (n=24, 24)	16 Participants	17 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Within 12-18 Months of Follow-up (n=17, 17)	11 Participants	9 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Within 18-24 Months of Follow-up (n=10, 9)	5 Participants	8 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Within 24-30 Months of Follow-up (n=4, 6)	2 Participants	5 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion Within 36-42 Months of Follow-up (n=0, 0)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion After 42 Months of Follow-up (n=0, 0)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 4 years, 5 months

Population: Participants from the Safety Evaluable Population, all randomized participants who received at least one dose of study drug, with B-Cell depletion.

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 a CD19 result ≥ 0.07 × 10\^9/L, where CD19 was previously depleted. B-cell recovery was only considered possible following the last dose of study treatment. The number of participants with B-cell recovery from End of Treatment to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) \[PD before B-cell recovery or PD within 45 days after recovery\] 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.

Outcome measures

Outcome measures
Measure	Obinutuzumab 1000 mg n=40 Participants Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 Participants Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery Up to 6 Months FU: Recovery with PD (n=30, 31)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery Up to 6 Months FU: Recovery without PD (n=30, 31)	2 Participants	3 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 6-12 Months FU: Recovery with PD (n=24, 24)	1 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 6-12 Months FU: Recovery without PD (n=24, 24)	7 Participants	7 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 12-18 Months FU: Recovery with PD (n=17, 17)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 12-18 Months FU: Recovery without PD (n=17, 17)	6 Participants	8 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 18-24 Months FU: Recovery with PD (n=10, 9)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 18-24 Months FU: Recovery without PD (n=10, 9)	5 Participants	1 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 24-30 Months FU: Recovery with PD (n=4, 6)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 24-30 Months FU: Recovery without PD (n=4, 6)	2 Participants	1 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 30-36 Months FU: Recovery with PD (n=1, 3)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 30-36 Months FU: Recovery without PD (n=1, 3)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 36-42 Months FU: Recovery with PD (n=0, 0)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery 36-42 Months FU: Recovery without PD (n=0, 0)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery After 42 Months FU: Recovery with PD (n=0, 0)	0 Participants	0 Participants
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery After 42 Months FU: Recovery without PD (n=0, 0)	0 Participants	0 Participants

Adverse Events

Obinutuzumab 1000 mg

Serious events: 8 serious events

Other events: 40 other events

Deaths: 0 deaths

Obinutuzumab 2000 mg

Serious events: 8 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Obinutuzumab 1000 mg n=40 participants at risk Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 participants at risk Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Blood and lymphatic system disorders Febrile neutropenia	5.0% 2/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Blood and lymphatic system disorders Neutropenia	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Infections and infestations Sepsis	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Infections and infestations Sinusitis	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Infections and infestations Urinary tract infection	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Infections and infestations Urosepsis	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Cardiac disorders Acute coronary syndrome	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Cardiac disorders Myocardial infarction	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Cardiac disorders Sinus bradycardia	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Injury, poisoning and procedural complications Infusion related reaction	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Injury, poisoning and procedural complications Fall	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
General disorders Chest pain	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
General disorders Pyrexia	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Nervous system disorders Depressed level of consciousness	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Hypoxia	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Vascular disorders Hypotension	2.5% 1/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Emphysema	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Injury, poisoning and procedural complications Rib fracture	0.00% 0/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months

Other adverse events

Other adverse events
Measure	Obinutuzumab 1000 mg n=40 participants at risk Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.	Obinutuzumab 2000 mg n=38 participants at risk Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Injury, poisoning and procedural complications Infusion related reaction	75.0% 30/40 • Up to 4 years, 5 months	63.2% 24/38 • Up to 4 years, 5 months
General disorders Pyrexia	40.0% 16/40 • Up to 4 years, 5 months	47.4% 18/38 • Up to 4 years, 5 months
General disorders Fatigue	40.0% 16/40 • Up to 4 years, 5 months	31.6% 12/38 • Up to 4 years, 5 months
General disorders Chills	20.0% 8/40 • Up to 4 years, 5 months	18.4% 7/38 • Up to 4 years, 5 months
General disorders Oedema peripheral	15.0% 6/40 • Up to 4 years, 5 months	15.8% 6/38 • Up to 4 years, 5 months
Gastrointestinal disorders Nausea	37.5% 15/40 • Up to 4 years, 5 months	26.3% 10/38 • Up to 4 years, 5 months
Gastrointestinal disorders Vomiting	27.5% 11/40 • Up to 4 years, 5 months	13.2% 5/38 • Up to 4 years, 5 months
Gastrointestinal disorders Diarrhoea	7.5% 3/40 • Up to 4 years, 5 months	18.4% 7/38 • Up to 4 years, 5 months
Gastrointestinal disorders Constipation	7.5% 3/40 • Up to 4 years, 5 months	13.2% 5/38 • Up to 4 years, 5 months
Nervous system disorders Dizziness	25.0% 10/40 • Up to 4 years, 5 months	18.4% 7/38 • Up to 4 years, 5 months
Nervous system disorders Headache	27.5% 11/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
Blood and lymphatic system disorders Neutropenia	35.0% 14/40 • Up to 4 years, 5 months	31.6% 12/38 • Up to 4 years, 5 months
Blood and lymphatic system disorders Thrombocytopenia	22.5% 9/40 • Up to 4 years, 5 months	18.4% 7/38 • Up to 4 years, 5 months
Blood and lymphatic system disorders Anaemia	17.5% 7/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Vascular disorders Flushing	20.0% 8/40 • Up to 4 years, 5 months	23.7% 9/38 • Up to 4 years, 5 months
Vascular disorders Hypotension	15.0% 6/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
Infections and infestations Upper respiratory tract infection	12.5% 5/40 • Up to 4 years, 5 months	15.8% 6/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.0% 6/40 • Up to 4 years, 5 months	28.9% 11/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Cough	15.0% 6/40 • Up to 4 years, 5 months	21.1% 8/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Rash	7.5% 3/40 • Up to 4 years, 5 months	15.8% 6/38 • Up to 4 years, 5 months
Psychiatric disorders Insomnia	15.0% 6/40 • Up to 4 years, 5 months	18.4% 7/38 • Up to 4 years, 5 months
General disorders Chest discomfort	7.5% 3/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
General disorders Asthenia	7.5% 3/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
General disorders Influenza like illness	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Injury, poisoning and procedural complications Contusion	0.00% 0/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Injury, poisoning and procedural complications Laceration	5.0% 2/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Gastrointestinal disorders Abdominal pain	7.5% 3/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
Gastrointestinal disorders Dyspepsia	2.5% 1/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 2/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Gastrointestinal disorders Abdominal discomfort	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Gastrointestinal disorders Dry mouth	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Nervous system disorders Dysgeusia	5.0% 2/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Nervous system disorders Tremor	5.0% 2/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Nervous system disorders Memory impairment	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Nervous system disorders Somnolence	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Nervous system disorders Syncope	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Bone pain	5.0% 2/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Muscle spasms	5.0% 2/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Myalgia	7.5% 3/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Back pain	7.5% 3/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 4/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Neck pain	7.5% 3/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 2/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 3/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.5% 1/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Hyperhidrosis	7.5% 3/40 • Up to 4 years, 5 months	10.5% 4/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Night sweats	5.0% 2/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Pruritus	7.5% 3/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Erythema	0.00% 0/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Alopecia	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Infections and infestations Urinary tract infection	5.0% 2/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Infections and infestations Sinusitis	5.0% 2/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Infections and infestations Fungal skin infection	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Infections and infestations Rhinitis	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Psychiatric disorders Depression	5.0% 2/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Metabolism and nutrition disorders Decreased appetite	10.0% 4/40 • Up to 4 years, 5 months	7.9% 3/38 • Up to 4 years, 5 months
Metabolism and nutrition disorders Hyperglycaemia	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Eye disorders Lacrimation increased	2.5% 1/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Eye disorders Visual impairment	2.5% 1/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Renal and urinary disorders Nocturia	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Ear and labyrinth disorders Vertigo	5.0% 2/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Investigations Blood magnesium decreased	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
Injury, poisoning and procedural complications Fall	2.5% 1/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months
General disorders Chest Pain	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Blood and lymphatic system disorders Febrile Neutropenia	5.0% 2/40 • Up to 4 years, 5 months	2.6% 1/38 • Up to 4 years, 5 months
Respiratory, thoracic and mediastinal disorders Hypoxia	5.0% 2/40 • Up to 4 years, 5 months	0.00% 0/38 • Up to 4 years, 5 months
Eye disorders Vision Blurred	0.00% 0/40 • Up to 4 years, 5 months	5.3% 2/38 • Up to 4 years, 5 months

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER