A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)

Follicular Lymphoma Clinical Trial

— ROMULUS  

Official title:

A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of Pinatuzumab Vedotin (DCDT2980S) in Combination With Rituximab or Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab and a Non-Randomized Phase Ib/II Evaluation of Polatuzumab Vedotin in Combination With Obinutuzumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01691898
• Other study ID #: GO27834
• Secondary ID: 2011-004377-84
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 27, 2012
• Est. completion date: February 7, 2019

Study information

• Verified date: February 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 231
• Est. completion date: February 7, 2019
• Est. primary completion date: March 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

• Life expectancy of at least 12 weeks

• History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL

• Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment

• Have a clinical indication for treatment as determined by the investigator

• Must have at least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or Magnetic Resonance Imaging [MRI])

Exclusion Criteria:

• Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start

• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start

• Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (</=) 2 prior study start

• Completion of autologous stem cell transplant (SCT) within 100 days prior study start

• Prior allogeneic SCT

• Eligibility for autologous SCT (participants with r/r DLBCL)

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)

• History of other malignancy that could affect compliance with the protocol or interpretation of results

• Current or past history of central nervous system lymphoma

• Current Grade >1 peripheral neuropathy

• Vaccination with a live vaccine within 28 days prior to treatment

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Obinutuzumab
Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.
• Pinatuzumab Vedotin
Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.
• Polatuzumab Vedotin
Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.
• Rituximab
RTX 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
France	Hopital Claude Huriez - CHU Lille	Lille
France	CHU Montpellier - Saint ELOI	Montpellier
France	Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Centre Henri Becquerel; Hematologie	Rouen
Germany	Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V	Heidelberg
Germany	Universitätsmedizin Johannes Gutenberg Universität; Klinik u. Poliklinik f. Neurologie	Mainz
Germany	Klinikum d.Universität München Campus Großhadern	München
Italy	A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna	Bologna	Emilia-Romagna
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Italy	Azienda Ospedale San Giovanni	Torino	Piemonte
Netherlands	Academisch Medisch Centrum; Hematologie	Amsterdam
United States	Univ of Michigan Med School; Hematology Oncology	Ann Arbor	Michigan
United States	Roswell Park Cancer Inst.	Buffalo	New York
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Texas Oncology-Baylor Sammons Cancer Center	Dallas	Texas
United States	Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center	Denver	Colorado
United States	Willamette Valley Cancer Ctr - 520 Country Club	Eugene	Oregon
United States	Fairfax N Virginia Hem/Onc PC	Fairfax	Virginia
United States	Florida Cancer Specialists - Fort Myers (Colonial Center Dr)	Fort Myers	Florida
United States	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Univ of Wisconsin-Madison	Madison	Wisconsin
United States	Hematology Oncology Associates; Carol G. Simon Ctr	Morristown	New Jersey
United States	Regional Cancer Care Associates LLC - Morristown	Morristown	New Jersey
United States	Sarah Cannon Cancer Center - Tennessee Oncology, Pllc	Nashville	Tennessee
United States	New York University Cancer Cen	New York	New York
United States	Oregon Health Sciences Uni	Portland	Oregon
United States	Oncology & Hematolgy Associates of SW Va Inc. - Roanoke	Roanoke	Virginia
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Texas Transplant Inst.	San Antonio	Texas
United States	Florida Cancer Specialists; Sarasota	Sarasota	Florida
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California
United States	Texas Oncology, P.A. - Tyler; Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver	Vancouver	Washington
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments greater than or equal to (>/=) 4 weeks after initial documentation. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50 percent (%) decrease in sum of the products of greatest diameters (SPD) of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. Participants with insufficient data to determine response were classified as non-responders.	Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)
Primary	Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014). DOR was defined as the time from the initial documentation of a CR or PR to the time of PD or death. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.	First occurrence of objective response up to PD/relapse or death due to any cause, whichever occurred first (up to approximately 3.5 years)
Primary	Percentage of Participants With CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) Per Lugano 2014 Response Criteria: Cohorts E, G, and H	Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin	Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against pinatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.	Baseline, post-baseline (up to approximately 5.5 years)
Secondary	Number of Participants With ADA to Polatuzumab Vedotin	Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against polatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.	Baseline, post-baseline (up to approximately 5.5 years)
Secondary	Number of Participants With ADA to Obinutuzumab	Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against obinutuzumab at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.	Baseline, post-baseline (up to approximately 5.5 years)
Secondary	Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)	Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Secondary	Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Secondary	Percentage of Participants Who Died Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)	Percentage of participants who died due to any cause was reported.	Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Secondary	Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C)	OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Secondary	Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)	Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)	Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by the Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)	Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)	Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. CR was defined as reduction of longest transverse diameter (LDi) of target nodes/nodal masses to less than or equal to (	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)	Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. CR was defined as reduction of LDi of target nodes/nodal masses to	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)	Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)	Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to	6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary	Percentage of Participants With Best OR Based on PET/CT or CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)	Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT or CT scan. Best OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake	Baseline up to disease progression or death, whichever occurred first (up to approximately 5.5 years)
Secondary	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	AUCinf for rituximab was estimated from serum concentration data using non-compartmental analysis.	Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Secondary	Maximum Observed Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	Cmax for rituximab was estimated from serum concentration data using non-compartmental analysis.	Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Secondary	Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	CL for rituximab was estimated from serum concentration data using non-compartmental analysis.	Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Secondary	Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	t1/2 for rituximab was estimated from serum concentration data using non-compartmental analysis.; Time Frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, & 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days).	Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description)
Secondary	Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	Vss for rituximab was estimated from serum concentration data using non-compartmental analysis.; Time Frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, & 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days)	Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description)
Secondary	AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	AUCinf of total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with Monomethyl Auristatin E (MMAE)-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	AUCinf of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. Antibody conjugated MMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Area Under the Concentration-Time Curve From Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	AUClast of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	Cmax of total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	Cmax of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	Cmax of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab	Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab	AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab	AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab	AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab	Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab	Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab	Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab	AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab	AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab	AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab	Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab	Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab	Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Cmax of Obinutuzumab: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)	Cmax of obinutuzumab was estimated from serum concentration data using non-compartmental analysis.	Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Secondary	Overall Survival (OS): Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)	OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Secondary	Percentage of Participants Who Died Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)	Percentage of participants who died due to any cause was reported.	Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Secondary	Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)	Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Secondary	Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)	Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.	Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 5.5 years)