A Study of Obinutuzumab in Chinese Participants With CD20+ Malignant Disease

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01680991
• Collaborator: (none)
• Enrollment: 48
• Locations: 4
• Arms: 3
• Duration (Months): 27
• Patients Per Site: 12
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This multi-center, open-label, single-arm study will evaluate the pharmacokinetics and safety of obinutuzumab in participants with cluster of differentiation (CD) 20 positive (+) malignant disease. Participants will receive multiple doses of obinutuzumab. The anticipated time on study treatment is 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia, Chronic, Diffuse Large B-cell Lymphoma, Follicular Lymphoma	Drug: Obinutuzumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Open Label, Single Arm, Multiple Dose Study to Assess the Pharmacokinetics of RO5072759 in Chinese Patients With CD20+ Malignant Disease
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CLL: 1000 mg Obinutuzumab Participants with chronic lymphocytic leukemia (CLL) will receive 1000 milligrams (mg) obinutuzumab as an intravenous (IV) infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. The first infusion on Cycle 1 Day 1 will be given over two days: Day 1 and Day 2. Additional doses of obinutuzumab will be administered on Cycle 1 Day 8 and Day 15.	Drug: Obinutuzumab; Multiple doses of obinutuzumab.; Other Names: RO5072759 GA101
Experimental: DLBCL: 1000 mg Obinutuzumab Participants with diffuse large B-cell lymphoma (DLBCL) will receive 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab will be administered on Cycle 1 Day 8 and Day 15.	Drug: Obinutuzumab; Multiple doses of obinutuzumab.; Other Names: RO5072759 GA101
Experimental: FL: 1000 mg Obinutuzumab Participants with follicular lymphoma (FL) will receive 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab will be administered on Cycle 1 Day 8 and Day 15.	Drug: Obinutuzumab; Multiple doses of obinutuzumab.; Other Names: RO5072759 GA101

Outcome Measures

Primary Outcome Measures

1. Area Under the Serum Concentration Time Curve From Zero to Day 7 (AUC0-7) of Obinutuzumab on Day 1, Cycle 1 [Cycle 1-NHL: within 2 hours (h) pre-dose (Pr-D), end of infusion (EoI), 4, 24, 72 and 120 h post-infusion (Po-I) on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8]

   DLBCL and FL are sub-types of Non-Hodgkin's Lymphoma (NHL) and time frame for these 2 groups was presented under NHL. For CLL, pharmacokinetic (PK) parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.

2. Maximum Observed Serum Concentration (Cmax) of Obinutuzumab on Day 1, Cycle 1 [Cycle 1-NHL: within 2 h Pr-D, EoI, 4, 24, 72 and 120 h Po-I on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8]

   DLBCL and FL are sub-types of NHL and time frame for these 2 groups was presented under NHL. For CLL, PK parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.

3. Area Under the Serum Concentration Versus Time Curve From 0 to Day 21 (AUC0-21) of Obinutuzumab at Cycle 8 [Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1]

4. Cmax of Obinutuzumab at Cycle 8 [Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1]

Secondary Outcome Measures

1. Time to Maximum Observed Serum Concentration (Tmax) of Obinutuzumab at Cycle 8 [Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1]

2. Apparent Terminal Half-life (t1/2) [Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1, 4-week follow-up (Day 29), 3 and 6 months after Cycle 8 dosing]

   Half-life is the time measured for the serum concentration of study drug to decrease (Dec) by one half.

3. Volume of Distribution at Steady State (Vss) of Obinutuzumab at Cycle 8 [Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1]

   Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

4. Total Systemic Clearance at Steady State (CLss) of Obinutuzumab at Cycle 8 [Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1]

   Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

5. Minimum Observed Serum Concentration of Obinutuzumab [Within 2 hours Pr-D on Day 1 of Cycles 2-8 and on Days 8,15 of Cycle 1]

6. Percentage of Participants With Complete Response (CR), CR Unconfirmed (CRu) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria [1 month after the last dose (received on Day 148) of study drug]

   CR: 1) Disappearance of clinical and radiographic evidence of disease, related symptoms and normalization of biochemical abnormalities definitely assignable to NHL, 2) Lymph nodes (LN) and nodal masses regressed to normal size after therapy (AT) (≤1.5 centimeters [cm] in their greatest transverse diameter [GTD] for LN greater than (>) 1.5 cm before therapy [BT]). LN that were 1.1 to 1.5 cm in their GTD BT decreased to ≤1 cm in GTD AT, or >75% in the sum of the products (SPD) of the GTD, 3) Enlarged spleen regressed in size and not palpable, 4) Absence of macroscopic nodules, 5) Enlarged organs decreased in size, and 6) If the bone marrow (BM) was involved, the infiltrate must be cleared on repeat BM aspirate and biopsy. CRu included those participants who met CR Criteria 1 and 3, but with 1 or more of the following features: a) A residual LN mass >1.5 cm in GTD that has regressed by more than 75% in their SPD, and b) Indeterminate BM (increased [Inc] number or size of aggregates).

7. Percentage of Participants With Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria [1 month after the last dose (received on Day 148) of study drug]

   PR: 1) ≥50% decrease in SPD of the 6 largest dominant nodes/nodal masses. These nodes or masses selected according to the following features: a) clearly measurable in ≥2 perpendicular dimensions, b) from as disparate regions of the body as possible, and c) included mediastinal and retroperitoneal areas of disease. 2) No increase in size of other nodes (liver/spleen). 3) Splenic and hepatic nodules regressed by ≥50% in SPD. 4) With exception of splenic and hepatic nodules, involvement of other organs was considered assessable and not measurable disease. 5) BM assessment is irrelevant for determination of a PR because it was assessable and not measurable disease; however, if positive, the cell type was specified. 6) No new sites of disease. PD requires the following: 1) ≥50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders. 2) Appearance of any new lesion during or at the end of therapy. SD is defined as less than a PR but not PD.

8. Percentage of Participants With Best Overall Response (BOR) of CR, CRu at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria [From screening to up to 1 month after the last dose (received on Day 148) of study drug]

   CR: 1) Disappearance of clinical and radiographic evidence of disease, related symptoms and normalization of biochemical abnormalities definitely assignable to NHL, 2) LN and nodal masses regressed to normal size AT (≤1.5 cm] in their GTD for LN >1.5 cm BT). LN that were 1.1 to 1.5 cm in their GTD BT decreased to ≤1 cm in GTD AT, or >75% in the SPD of the GTD, 3) Enlarged spleen regressed in size and not palpable, 4) Absence of macroscopic nodules in any organs, 5) Enlarged organs decreased in size, and 6) If the BM was involved, the infiltrate must be cleared on repeat BM aspirate and biopsy. CRu included those participants who met CR Criteria 1 and 3, but with 1 or more of the following features: a) A residual LN mass >1.5 cm in GTD that has regressed by more than 75% in their SPD, b) Indeterminate BM (increased number or size of aggregates).

9. Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria [From screening to up to 1 month after the last dose (received on Day 148) of study drug]

   PR: 1) ≥50% decrease in SPD of the 6 largest dominant nodes/nodal masses. These nodes or masses selected according to the following features: a) clearly measurable in ≥2 perpendicular dimensions, b) from as disparate regions of the body as possible, and c) included mediastinal and retroperitoneal areas of disease. 2) No increase in size of other nodes (liver/spleen). 3) Splenic and hepatic nodules regressed by ≥50% in SPD. 4) With exception of splenic and hepatic nodules, involvement of other organs was considered assessable and not measurable disease. 5) BM assessment is irrelevant for determination of a PR because it was assessable and not measurable disease; however, if positive, the cell type was specified. 6) No new sites of disease. PD requires the following: 1) ≥50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders. 2) Appearance of any new lesion during or at the end of therapy. SD is defined as less than a PR but not PD.

10. Percentage of Participants With Complete Remission (CRe), CRe With Incomplete BM Recovery (CRi) at End of Treatment (1 Month After Cycle 8) in CLL Participants According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines [2 months after the last dose (received on Day 148) of study drug]

    CRe required the following criteria as assessed, at least 2 months from completing therapy: a) peripheral blood lymphocytes (PBL) less than (<) 4 x 10^9/L, b) Absence of significant lymphadenopathy (LD) by physical examination (PE), c) No hepatomegaly/splenomegaly (HM/SM) by PE, d) Absence of constitutional symptoms and e) Blood counts above the following values (i. Neutrophils [Neu] >1.5 x 10^9/L without the need for exogenous growth factors [EGF], ii. Platelets (Plt) >100 x 10^9/L without the need for EGF, and iii. Hemoglobin (Hb) >11.0 g/dL without blood transfusion or need for erythropoietin), and d) Once clinical and laboratory reports demonstrated CRe, a BM aspirate and biopsy was performed at least 2 months after the last treatment; to define a CRe, BM sample should be normocellular for age, <30% of the cells being PBL and lymphoid nodules absent. CRi: CRe but persistent anemia/thrombocytopenia/neutropenia unrelated to CLL, but related to drug toxicity.

11. Percentage of Participants With PR, SD, and PD at End of Treatment (1 Month After Cycle 8) in CLL Participants According to IWCLL 2008 Guidelines [2 months after the last dose (received on Day 148) of study drug]

    Group A: a)Dec LN size by ≥50% either in SPD of 6 LN or largest diameter of enlarged LN (ELN) detected BT, b)Reduction (Red) in BT enlargement of liver, c)Red in BT enlargement of spleen, d)Dec in PBL by ≥50% from baseline, e)A 50% Red in BM infiltrate or B-lymphoid nodules in BM and f)No Inc in any LN and no new ELN. Group B: a)Plt count=100,000/µL or Inc of ≥50% over baseline, b)Hb >11 g/dL or ≥50% Inc over baseline, c)Neu > 1500/µL or > 50% Inc over baseline. PR is considered as achieved if 2 of Group A criteria and 1 of Group B criteria were met for ≥2 months. PD is defined as LD (appearance of new lesion [ELN], SM, HM or other organ infiltrates) or Inc by ≥50% in greatest determined diameter of any previous site or Inc in previously noted enlargement of liver/spleen by ≥50% or new appearance of HM/SM or an Inc in number of PBL ≥50% or transformation to a more aggressive histology or occurrence of cytopenia attributable to CLL. SD is defined as less than a PR but is not PD.

12. Percentage of Participants With BOR of CRe, CRi at Anytime During the Study in CLL Participants According to IWCLL 2008 Guidelines [From screening to up to 2 months after the last dose (received on Day 148) of study drug]

    CRe required the following criteria as assessed, at least 2 months from completing therapy: a) PBL <4 x 10^9/L, b) Absence of significant LD by PE, c) No HM/SM by PE, d) Absence of constitutional symptoms and e) Blood counts above the following values (i. Neu >1.5 x 10^9/L without the need for EGF, ii. Plt >100 x 10^9/L without the need for EGF, and iii. Hb >11.0 g/dL without blood transfusion or need for EGF, and d) Once clinical and laboratory reports demonstrated CRe, a BM aspirate and biopsy was performed at least 2 months after the last treatment; to define a CRe, BM sample should be normocellular for age, <30% of the cells being PBL and lymphoid nodules absent. CRi: CRe but persistent anemia/thrombocytopenia/neutropenia unrelated to CLL, but related to drug toxicity.

13. Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in CLL Participants According to IWCLL 2008 Guidelines [From screening to up to 2 months after the last dose (received on Day 148) of study drug]

    Group A: a)Dec LN size by ≥50% either in SPD of 6 LN or largest diameter of ELN detected BT, b)Red in BT enlargement of liver, c)Red in BT enlargement of spleen, d)Dec in PBL by ≥50% from baseline, e)A 50% Red in BM infiltrate or B-lymphoid nodules in BM and f)No Inc in any LN and no new ELN. Group B: a)Plt count=100,000/µL or Inc of ≥50% over baseline, b)Hb >11 g/dL or ≥50% Inc over baseline, c)Neu > 1500/µL or > 50% Inc over baseline. PR is considered as achieved if 2 of Group A criteria and 1 of Group B criteria were met for ≥2 months. PD is defined as LD (appearance of new lesion [ELN], SM, HM or other organ infiltrates) or Inc by ≥50% in greatest determined diameter of any previous site or Inc in previously noted enlargement of liver/spleen by ≥50% or new appearance of HM/SM or an Inc in number of PBL ≥50% or transformation to a more aggressive histology or occurrence of cytopenia attributable to CLL. SD is defined as less than a PR but is not PD.

14. Number of Participants With Positive Human Anti-Human Antibodies (HAHA) [Cycle 1 (Day 1), Cycle 4 (Day 1), 4-week follow-up, 3 and 6 month follow-up]

    For the detection of HAHA, serum samples were initially analyzed using a validated enzyme linked immunosorbent assay (ELISA) method (screening assay, tier 1). The lower limit of quantification (LLOQ) in undiluted serum was 18.4 nanograms per milliliter (ng/mL). The precision ranged from 4.85 percent (%) to 16.0%. In serum samples found positive, the presence of specific anti-obinutuzumab antibodies was confirmed or excluded using the same ELISA method with an appropriate immunocompetition step (addition of excess obinutuzumab, confirmation assay, tier 2). Samples were confirmed as containing specific anti-obinutuzumab antibodies if there was a signal reduction ≥85.7% in the presence of obinutuzumab.

15. Number of Participants With Positive Human Anti-Chimeric Antibodies (HACA) [Cycle 1, Day 1]

    Serum concentrations of HACA against rituximab were determined by ELISA. The LLOQ in undiluted serum was 5.00 relative units per milliliter (RU/mL). The precision and accuracy of the assay, as determined from the analysis of quality control samples, were satisfactory throughout the study; precision ranged from 6.4% to 13.6% and accuracy ranged from 88.2% to 94.8%.

16. Number of Participants With B-cell Depletion or Recovery [Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year]

    Depletion is defined as cluster of differentiation (CD) 19+ B-cell count <0.07 x10^9/L.Recovery is defined as CD19+ B-cell equal to or greater than 0.07 x 10^9/L.

17. Duration of Depletion of CD19+ B-cell [Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year]

    Depletion is defined as CD19+ B-cell count < 0.07 x 10^9/L. The duration of depletion is defined as the number of days between first assessment of B-cell depletion and the first assessment where CD19+ cell count returned to at least the depletion level from baseline and not followed by any further B-cell depletion. If participant did not return to above depletion level, then the cut off is at the time of last assessment.

18. Time to Recovery of CD19+ B-cell [Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year]

    Recovery is defined as CD19+ B-cell equal to or greater than 0.07 x 10^9/L. Time to recovery is defined as time between the beginning of depletion and first value after end of treatment that is equal or above 0.07x10^9/L and not exclusively followed by depleted values only. If participant did not return to above recovery level then set to Null.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of CD20+ B-cell lymphoma or B-CLL

• Refractory/relapsed CLL, FL, and DLBCL

• At least 1 measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension) with the exception of CLL

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy >6 months

Exclusion Criteria:

• Prior use of any investigational antibody therapy within 6 months of study start

• Prior use of any anti-cancer vaccine

• Prior administration of rituximab within 3 months of study start

• Prior administration of radioimmunotherapy 3 months prior to study entry

• Central nervous system lymphoma

• History of other malignancy

• Evidence of significant, uncontrolled concomitant disease

• Abnormal laboratory values

• Patients with progressive multifocalleukoencephalopathy (PML)

• Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China	100021
2		Beijing		China	100142
3		Guangzhou		China
4		Shanghai		China	200025

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: NCT01680991
• Other Study ID Numbers: YP25623
• First Posted: Sep 7, 2012
• Last Update Posted: Apr 25, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Obinutuzumab

Study Results

Participant Flow

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with chronic lymphocytic leukemia (CLL) received 1000 milligrams (mg) obinutuzumab as an intravenous (IV) infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with diffuse large B-cell lymphoma (DLBCL) received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with follicular lymphoma (FL) received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Period Title: Overall Study
STARTED	12	23	13
COMPLETED	4	4	9
NOT COMPLETED	8	19	4

Baseline Characteristics

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab	Total
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Total of all reporting groups
Overall Participants	12	23	13	48
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.7 (12.0)	53.3 (15.8)	55.1 (8.8)	55.6 (13.4)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	12 52.2%	5 38.5%	22 45.8%
Male	7 58.3%	11 47.8%	8 61.5%	26 54.2%

Outcome Measures

1. Primary Outcome

Title	Area Under the Serum Concentration Time Curve From Zero to Day 7 (AUC0-7) of Obinutuzumab on Day 1, Cycle 1
Description	DLBCL and FL are sub-types of Non-Hodgkin's Lymphoma (NHL) and time frame for these 2 groups was presented under NHL. For CLL, pharmacokinetic (PK) parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.
Time Frame	Cycle 1-NHL: within 2 hours (h) pre-dose (Pr-D), end of infusion (EoI), 4, 24, 72 and 120 h post-infusion (Po-I) on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8

Outcome Measure Data

Analysis Population Description

PK analysis population included all participants who received at least 1 dose of study drug and had serum concentrations available. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	11	21	13
Geometric Mean (Geometric Coefficient of Variation) [day*micrograms per milliliter]	1458 (34.8)	1750 (20.5)	1647 (20.7)

2. Primary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Obinutuzumab on Day 1, Cycle 1
Description	DLBCL and FL are sub-types of NHL and time frame for these 2 groups was presented under NHL. For CLL, PK parameters were from Cycle 1 Day 1 and Day 2 dosing, due to split dosing.
Time Frame	Cycle 1-NHL: within 2 h Pr-D, EoI, 4, 24, 72 and 120 h Po-I on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	11	21	13
Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliter (mcg/mL)]	369 (31.8)	442 (21.1)	437 (16.7)

3. Primary Outcome

Title	Area Under the Serum Concentration Versus Time Curve From 0 to Day 21 (AUC0-21) of Obinutuzumab at Cycle 8
Time Frame	Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	8	11
Geometric Mean (Geometric Coefficient of Variation) [day*mcg/mL]	12289 (42.7)	13000 (37.3)	11285 (26.7)

4. Primary Outcome

Title	Cmax of Obinutuzumab at Cycle 8
Time Frame	Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	8	11
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	1050 (32.6)	966 (28.3)	867 (19.6)

5. Secondary Outcome

Title	Time to Maximum Observed Serum Concentration (Tmax) of Obinutuzumab at Cycle 8
Time Frame	Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	8	11
Median (Full Range) [hours]	3.5	7.25	4.0

6. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2)
Description	Half-life is the time measured for the serum concentration of study drug to decrease (Dec) by one half.
Time Frame	Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1, 4-week follow-up (Day 29), 3 and 6 months after Cycle 8 dosing

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	6	11
Geometric Mean (Geometric Coefficient of Variation) [day]	21.5 (71.8)	33.3 (68.6)	26.7 (49.6)

7. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of Obinutuzumab at Cycle 8
Description	Vss reflects the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.
Time Frame	Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	6	11
Geometric Mean (Geometric Coefficient of Variation) [Liter]	3.32 (27.9)	4.49 (38.2)	4.03 (21.5)

8. Secondary Outcome

Title	Total Systemic Clearance at Steady State (CLss) of Obinutuzumab at Cycle 8
Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame	Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1

Outcome Measure Data

Analysis Population Description

PK analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	8	11
Geometric Mean (Geometric Coefficient of Variation) [mL/day]	81.4 (42.7)	76.9 (37.3)	88.6 (26.7)

9. Secondary Outcome

Title	Minimum Observed Serum Concentration of Obinutuzumab
Time Frame	Within 2 hours Pr-D on Day 1 of Cycles 2-8 and on Days 8,15 of Cycle 1

Outcome Measure Data

Analysis Population Description

PK population. Here, number of participants analyzed = participants who were evaluable for this outcome and "n" is the number of participants evaluable at the specified time point.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	11	22	13
Cycle 1-Day 8 (n=11,22,13)	156 (57.2)	186 (25.2)	148 (39.2)
Cycle 1-Day 15 (n=11,22,13)	282 (69.4)	350 (23.7)	284 (26.5)
Cycle 2 (n=11,21,13)	389 (71.2)	458 (26.3)	433 (31.2)
Cycle 3 (n=10,18,13)	260 (246)	367 (49.6)	346 (31)
Cycle 4 (n=10,14,13)	232 (279.7)	370 (49.2)	346 (31)
Cycle 5 (n=9,11,11)	299 (91.2)	412 (42)	396 (44.8)
Cycle 6 (n=9,10,11)	317 (93.5)	425 (38.2)	361 (40.6)
Cycle 7 (n=9,10,11)	358 (80.6)	367 (40.3)	375 (41.3)
Cycle 8 (n=9,8,11)	403 (85.3)	455 (45.4)	352 (38.4)

10. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR), CR Unconfirmed (CRu) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
Description	CR: 1) Disappearance of clinical and radiographic evidence of disease, related symptoms and normalization of biochemical abnormalities definitely assignable to NHL, 2) Lymph nodes (LN) and nodal masses regressed to normal size after therapy (AT) (≤1.5 centimeters [cm] in their greatest transverse diameter [GTD] for LN greater than (>) 1.5 cm before therapy [BT]). LN that were 1.1 to 1.5 cm in their GTD BT decreased to ≤1 cm in GTD AT, or >75% in the sum of the products (SPD) of the GTD, 3) Enlarged spleen regressed in size and not palpable, 4) Absence of macroscopic nodules, 5) Enlarged organs decreased in size, and 6) If the bone marrow (BM) was involved, the infiltrate must be cleared on repeat BM aspirate and biopsy. CRu included those participants who met CR Criteria 1 and 3, but with 1 or more of the following features: a) A residual LN mass >1.5 cm in GTD that has regressed by more than 75% in their SPD, and b) Indeterminate BM (increased [Inc] number or size of aggregates).
Time Frame	1 month after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for DLBCL and FL arm groups.

Arm/Group Title	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	23	13
CR	0 0%	0 0%
CRu	4.3 35.8%	0 0%

11. Secondary Outcome

Title	Percentage of Participants With Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
Description	PR: 1) ≥50% decrease in SPD of the 6 largest dominant nodes/nodal masses. These nodes or masses selected according to the following features: a) clearly measurable in ≥2 perpendicular dimensions, b) from as disparate regions of the body as possible, and c) included mediastinal and retroperitoneal areas of disease. 2) No increase in size of other nodes (liver/spleen). 3) Splenic and hepatic nodules regressed by ≥50% in SPD. 4) With exception of splenic and hepatic nodules, involvement of other organs was considered assessable and not measurable disease. 5) BM assessment is irrelevant for determination of a PR because it was assessable and not measurable disease; however, if positive, the cell type was specified. 6) No new sites of disease. PD requires the following: 1) ≥50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders. 2) Appearance of any new lesion during or at the end of therapy. SD is defined as less than a PR but not PD.
Time Frame	1 month after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for DLBCL and FL arm groups.

Arm/Group Title	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	23	13
PR	8.7 72.5%	46.2 200.9%
SD	8.7 72.5%	30.8 133.9%
PD	65.2 543.3%	23.1 100.4%

12. Secondary Outcome

Title	Percentage of Participants With Best Overall Response (BOR) of CR, CRu at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
Description	CR: 1) Disappearance of clinical and radiographic evidence of disease, related symptoms and normalization of biochemical abnormalities definitely assignable to NHL, 2) LN and nodal masses regressed to normal size AT (≤1.5 cm] in their GTD for LN >1.5 cm BT). LN that were 1.1 to 1.5 cm in their GTD BT decreased to ≤1 cm in GTD AT, or >75% in the SPD of the GTD, 3) Enlarged spleen regressed in size and not palpable, 4) Absence of macroscopic nodules in any organs, 5) Enlarged organs decreased in size, and 6) If the BM was involved, the infiltrate must be cleared on repeat BM aspirate and biopsy. CRu included those participants who met CR Criteria 1 and 3, but with 1 or more of the following features: a) A residual LN mass >1.5 cm in GTD that has regressed by more than 75% in their SPD, b) Indeterminate BM (increased number or size of aggregates).
Time Frame	From screening to up to 1 month after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for DLBCL and FL arm groups.

Arm/Group Title	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	23	13
CR	0 0%	0 0%
CRu	4.3 35.8%	0 0%

13. Secondary Outcome

Title	Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
Description	PR: 1) ≥50% decrease in SPD of the 6 largest dominant nodes/nodal masses. These nodes or masses selected according to the following features: a) clearly measurable in ≥2 perpendicular dimensions, b) from as disparate regions of the body as possible, and c) included mediastinal and retroperitoneal areas of disease. 2) No increase in size of other nodes (liver/spleen). 3) Splenic and hepatic nodules regressed by ≥50% in SPD. 4) With exception of splenic and hepatic nodules, involvement of other organs was considered assessable and not measurable disease. 5) BM assessment is irrelevant for determination of a PR because it was assessable and not measurable disease; however, if positive, the cell type was specified. 6) No new sites of disease. PD requires the following: 1) ≥50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders. 2) Appearance of any new lesion during or at the end of therapy. SD is defined as less than a PR but not PD.
Time Frame	From screening to up to 1 month after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for DLBCL and FL arm groups.

Arm/Group Title	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	23	13
PR	21.7 180.8%	61.5 267.4%
SD	26.1 217.5%	30.8 133.9%
PD	39.1 325.8%	7.7 33.5%

14. Secondary Outcome

Title	Percentage of Participants With Complete Remission (CRe), CRe With Incomplete BM Recovery (CRi) at End of Treatment (1 Month After Cycle 8) in CLL Participants According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines
Description	CRe required the following criteria as assessed, at least 2 months from completing therapy: a) peripheral blood lymphocytes (PBL) less than (<) 4 x 10^9/L, b) Absence of significant lymphadenopathy (LD) by physical examination (PE), c) No hepatomegaly/splenomegaly (HM/SM) by PE, d) Absence of constitutional symptoms and e) Blood counts above the following values (i. Neutrophils [Neu] >1.5 x 10^9/L without the need for exogenous growth factors [EGF], ii. Platelets (Plt) >100 x 10^9/L without the need for EGF, and iii. Hemoglobin (Hb) >11.0 g/dL without blood transfusion or need for erythropoietin), and d) Once clinical and laboratory reports demonstrated CRe, a BM aspirate and biopsy was performed at least 2 months after the last treatment; to define a CRe, BM sample should be normocellular for age, <30% of the cells being PBL and lymphoid nodules absent. CRi: CRe but persistent anemia/thrombocytopenia/neutropenia unrelated to CLL, but related to drug toxicity.
Time Frame	2 months after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for CLL participants.

Arm/Group Title	CLL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.
Measure Participants	12
CRe	0 0%
CRi	0 0%

15. Secondary Outcome

Title	Percentage of Participants With PR, SD, and PD at End of Treatment (1 Month After Cycle 8) in CLL Participants According to IWCLL 2008 Guidelines
Description	Group A: a)Dec LN size by ≥50% either in SPD of 6 LN or largest diameter of enlarged LN (ELN) detected BT, b)Reduction (Red) in BT enlargement of liver, c)Red in BT enlargement of spleen, d)Dec in PBL by ≥50% from baseline, e)A 50% Red in BM infiltrate or B-lymphoid nodules in BM and f)No Inc in any LN and no new ELN. Group B: a)Plt count=100,000/µL or Inc of ≥50% over baseline, b)Hb >11 g/dL or ≥50% Inc over baseline, c)Neu > 1500/µL or > 50% Inc over baseline. PR is considered as achieved if 2 of Group A criteria and 1 of Group B criteria were met for ≥2 months. PD is defined as LD (appearance of new lesion [ELN], SM, HM or other organ infiltrates) or Inc by ≥50% in greatest determined diameter of any previous site or Inc in previously noted enlargement of liver/spleen by ≥50% or new appearance of HM/SM or an Inc in number of PBL ≥50% or transformation to a more aggressive histology or occurrence of cytopenia attributable to CLL. SD is defined as less than a PR but is not PD.
Time Frame	2 months after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for CLL participants

Arm/Group Title	CLL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.
Measure Participants	12
PR	58.3 485.8%
SD	8.3 69.2%
PD	16.7 139.2%

16. Secondary Outcome

Title	Percentage of Participants With BOR of CRe, CRi at Anytime During the Study in CLL Participants According to IWCLL 2008 Guidelines
Description	CRe required the following criteria as assessed, at least 2 months from completing therapy: a) PBL <4 x 10^9/L, b) Absence of significant LD by PE, c) No HM/SM by PE, d) Absence of constitutional symptoms and e) Blood counts above the following values (i. Neu >1.5 x 10^9/L without the need for EGF, ii. Plt >100 x 10^9/L without the need for EGF, and iii. Hb >11.0 g/dL without blood transfusion or need for EGF, and d) Once clinical and laboratory reports demonstrated CRe, a BM aspirate and biopsy was performed at least 2 months after the last treatment; to define a CRe, BM sample should be normocellular for age, <30% of the cells being PBL and lymphoid nodules absent. CRi: CRe but persistent anemia/thrombocytopenia/neutropenia unrelated to CLL, but related to drug toxicity.
Time Frame	From screening to up to 2 months after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for CLL participants.

Arm/Group Title	CLL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.
Measure Participants	12
CRe	0 0%
CRi	0 0%

17. Secondary Outcome

Title	Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in CLL Participants According to IWCLL 2008 Guidelines
Description	Group A: a)Dec LN size by ≥50% either in SPD of 6 LN or largest diameter of ELN detected BT, b)Red in BT enlargement of liver, c)Red in BT enlargement of spleen, d)Dec in PBL by ≥50% from baseline, e)A 50% Red in BM infiltrate or B-lymphoid nodules in BM and f)No Inc in any LN and no new ELN. Group B: a)Plt count=100,000/µL or Inc of ≥50% over baseline, b)Hb >11 g/dL or ≥50% Inc over baseline, c)Neu > 1500/µL or > 50% Inc over baseline. PR is considered as achieved if 2 of Group A criteria and 1 of Group B criteria were met for ≥2 months. PD is defined as LD (appearance of new lesion [ELN], SM, HM or other organ infiltrates) or Inc by ≥50% in greatest determined diameter of any previous site or Inc in previously noted enlargement of liver/spleen by ≥50% or new appearance of HM/SM or an Inc in number of PBL ≥50% or transformation to a more aggressive histology or occurrence of cytopenia attributable to CLL. SD is defined as less than a PR but is not PD.
Time Frame	From screening to up to 2 months after the last dose (received on Day 148) of study drug

Outcome Measure Data

Analysis Population Description

Safety analysis population. Data reported only for CLL participants.

Arm/Group Title	CLL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.
Measure Participants	12
PR	75.0 625%
SD	8.3 69.2%
PD	0 0%

18. Secondary Outcome

Title	Number of Participants With Positive Human Anti-Human Antibodies (HAHA)
Description	For the detection of HAHA, serum samples were initially analyzed using a validated enzyme linked immunosorbent assay (ELISA) method (screening assay, tier 1). The lower limit of quantification (LLOQ) in undiluted serum was 18.4 nanograms per milliliter (ng/mL). The precision ranged from 4.85 percent (%) to 16.0%. In serum samples found positive, the presence of specific anti-obinutuzumab antibodies was confirmed or excluded using the same ELISA method with an appropriate immunocompetition step (addition of excess obinutuzumab, confirmation assay, tier 2). Samples were confirmed as containing specific anti-obinutuzumab antibodies if there was a signal reduction ≥85.7% in the presence of obinutuzumab.
Time Frame	Cycle 1 (Day 1), Cycle 4 (Day 1), 4-week follow-up, 3 and 6 month follow-up

Outcome Measure Data

Analysis Population Description

Safety analysis population. "n" represents the number of participants who were evaluable at the specified time point.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	12	23	13
Cycle 1, Day 1 (n=12,23,13)	0 0%	0 0%	0 0%
Cycle 4, Day 1 (n=11,14,13)	0 0%	0 0%	0 0%
4 week follow-up (n=10,10,11)	0 0%	0 0%	0 0%
3 month follow-up (n=8,4,11)	0 0%	0 0%	0 0%
6 month follow-up (n=7,4,11)	0 0%	0 0%	1 7.7%

19. Secondary Outcome

Title	Number of Participants With Positive Human Anti-Chimeric Antibodies (HACA)
Description	Serum concentrations of HACA against rituximab were determined by ELISA. The LLOQ in undiluted serum was 5.00 relative units per milliliter (RU/mL). The precision and accuracy of the assay, as determined from the analysis of quality control samples, were satisfactory throughout the study; precision ranged from 6.4% to 13.6% and accuracy ranged from 88.2% to 94.8%.
Time Frame	Cycle 1, Day 1

Outcome Measure Data

Analysis Population Description

Safety analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	10	20	7
Number [participants]	2 16.7%	1 4.3%	0 0%

20. Secondary Outcome

Title	Number of Participants With B-cell Depletion or Recovery
Description	Depletion is defined as cluster of differentiation (CD) 19+ B-cell count <0.07 x10^9/L.Recovery is defined as CD19+ B-cell equal to or greater than 0.07 x 10^9/L.
Time Frame	Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year

Outcome Measure Data

Analysis Population Description

Safety analysis population.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	12	23	13
B-cell Depletion	9 75%	23 100%	13 100%
B-cell Recovery	4 33.3%	1 4.3%	1 7.7%

21. Secondary Outcome

Title	Duration of Depletion of CD19+ B-cell
Description	Depletion is defined as CD19+ B-cell count < 0.07 x 10^9/L. The duration of depletion is defined as the number of days between first assessment of B-cell depletion and the first assessment where CD19+ cell count returned to at least the depletion level from baseline and not followed by any further B-cell depletion. If participant did not return to above depletion level, then the cut off is at the time of last assessment.
Time Frame	Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year

Outcome Measure Data

Analysis Population Description

Safety analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	9	23	12
Mean (Standard Deviation) [days]	238.7 (182.5)	141.0 (167.5)	386.0 (176.0)

22. Secondary Outcome

Title	Time to Recovery of CD19+ B-cell
Description	Recovery is defined as CD19+ B-cell equal to or greater than 0.07 x 10^9/L. Time to recovery is defined as time between the beginning of depletion and first value after end of treatment that is equal or above 0.07x10^9/L and not exclusively followed by depleted values only. If participant did not return to above recovery level then set to Null.
Time Frame	Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year

Outcome Measure Data

Analysis Population Description

Safety analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome and "n" represents the number of participants evaluable for the specified category.

Arm/Group Title	CLL: 1000 mg Obinutuzumab	DLBCL: 1000 mg Obinutuzumab	FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.	Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.	Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
Measure Participants	4	1	1
Time to recovery with PD (n=1,0,1)	419 (NA)	NA (NA)	331.0 (NA)
Time to recovery without PD (n=3,1,0)	229.0 (87.5)	515.0 (NA)	NA (NA)

Adverse Events

Time Frame	Until 3 months after last study drug (Up to approximately 9 months)
Adverse Event Reporting Description	Safety analysis population.
Arm/Group Title	CLL: 1000 mg Obinutuzumab		DLBCL: 1000 mg Obinutuzumab		FL: 1000 mg Obinutuzumab
Arm/Group Description	Participants with CLL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15. The first infusion on Cycle 1 Day 1 was given over two days: Day 1- 100 mg and Day 2- 900 mg.		Participants with DLBCL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.		Participants with FL received 1000 mg obinutuzumab as an IV infusion, on Day 1 of each 21-day cycle for a maximum of 8 cycles. Additional doses of obinutuzumab were administered on Cycle 1 Day 8 and Day 15.
All Cause Mortality
	CLL: 1000 mg Obinutuzumab		DLBCL: 1000 mg Obinutuzumab		FL: 1000 mg Obinutuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CLL: 1000 mg Obinutuzumab		DLBCL: 1000 mg Obinutuzumab		FL: 1000 mg Obinutuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		3/23 (13%)		1/13 (7.7%)
Blood and lymphatic system disorders
Neutropenia	1/12 (8.3%)		0/23 (0%)		1/13 (7.7%)
Thrombocytopenia	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
General disorders
Submandibular mass	0/12 (0%)		1/23 (4.3%)		0/13 (0%)
Infections and infestations
Pneumonia	2/12 (16.7%)		0/23 (0%)		1/13 (7.7%)
Infected cyst	0/12 (0%)		1/23 (4.3%)		0/13 (0%)
Urinary tract infection	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Investigations
Platelet count decreased	0/12 (0%)		1/23 (4.3%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	CLL: 1000 mg Obinutuzumab		DLBCL: 1000 mg Obinutuzumab		FL: 1000 mg Obinutuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)		17/23 (73.9%)		7/13 (53.8%)
Blood and lymphatic system disorders
Anaemia	2/12 (16.7%)		0/23 (0%)		1/13 (7.7%)
Thrombocytopenia	2/12 (16.7%)		1/23 (4.3%)		0/13 (0%)
Lymph node pain	1/12 (8.3%)		1/23 (4.3%)		0/13 (0%)
Leukocytosis	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Leukopenia	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Neutropenia	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Eye disorders
Scleral haemorrhage	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Gastrointestinal disorders
Abdominal pain	0/12 (0%)		2/23 (8.7%)		0/13 (0%)
Diarrhoea	1/12 (8.3%)		0/23 (0%)		1/13 (7.7%)
Nausea	1/12 (8.3%)		1/23 (4.3%)		0/13 (0%)
Vomiting	0/12 (0%)		1/23 (4.3%)		1/13 (7.7%)
Dyspepsia	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Toothache	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
General disorders
Pyrexia	6/12 (50%)		3/23 (13%)		2/13 (15.4%)
Chills	3/12 (25%)		1/23 (4.3%)		0/13 (0%)
Chest discomfort	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Local swelling	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Infections and infestations
Nasopharyngitis	0/12 (0%)		2/23 (8.7%)		0/13 (0%)
Epididymitis	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Gingivitis	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Herpes zoster	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Influenza	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Urinary tract infection	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Injury, poisoning and procedural complications
Infusion related reaction	7/12 (58.3%)		5/23 (21.7%)		3/13 (23.1%)
Scratch	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Investigations
Alanine aminotransferase increased	0/12 (0%)		3/23 (13%)		0/13 (0%)
Aspartate aminotransferase increased	0/12 (0%)		3/23 (13%)		0/13 (0%)
Blood creatinine increased	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Blood pressure decreased	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Blood uric acid increased	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Heart rate decreased	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Neutrophil count decreased	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Platelet count decreased	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
White blood cell count decreased	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/12 (8.3%)		1/23 (4.3%)		0/13 (0%)
Muscular weakness	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Nervous system disorders
Tremor	1/12 (8.3%)		1/23 (4.3%)		0/13 (0%)
Extrapyramidal disorder	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Psychiatric disorders
Insomnia	1/12 (8.3%)		1/23 (4.3%)		0/13 (0%)
Renal and urinary disorders
Urinary retention	1/12 (8.3%)		0/23 (0%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	4/12 (33.3%)		1/23 (4.3%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/12 (0%)		1/23 (4.3%)		1/13 (7.7%)
Rash	0/12 (0%)		0/23 (0%)		1/13 (7.7%)
Vascular disorders
Hypertension	2/12 (16.7%)		1/23 (4.3%)		0/13 (0%)
Deep vein thrombosis	0/12 (0%)		0/23 (0%)		1/13 (7.7%)

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.