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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02257567




Registration number
NCT02257567
Ethics application status
Date submitted
2/10/2014
Date registered
6/10/2014
Date last updated
14/11/2022

Titles & IDs
Public title
A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
Scientific title
A Phase IB/II Study Evaluating The Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination With Rituximab (R) or Obinutuzumab (G) Plus Bendamustine (B) in Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
Secondary ID [1] 0 0
2014-001361-28
Secondary ID [2] 0 0
GO29365
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bendamustine
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Polatuzumab vedotin (Liquid)
Treatment: Drugs - Rituximab
Treatment: Drugs - Polatuzumab vedotin (Lyophilized)

Experimental: Arm A (Phase II Randomization): Polatuzumab+BR in FL - Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.

Active Comparator: Arm B (Phase II Randomization): BR in FL - Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.

Experimental: Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL - Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.

Active Comparator: Arm D (Phase II Randomization): BR in DLBCL - Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.

Experimental: Arm E (Phase II Expansion): Polatuzumab+BG in FL - Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.

Experimental: Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL - Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.

Experimental: Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL - Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.

Experimental: Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL - Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.

Experimental: Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL - Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.

Experimental: Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL - Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.

Experimental: Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL - In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.

Experimental: Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL - In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.


Treatment: Drugs: Bendamustine
Bendamustine 90 milligrams per meter-squared (mg/m^2) per day administered IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Treatment: Drugs: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Treatment: Drugs: Polatuzumab vedotin (Liquid)
Polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) administered IV on Day 2 of Cycle 1, then on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Treatment: Drugs: Rituximab
Rituximab standard dose, 375 mg/m^2 IV on Day 1 of each cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Treatment: Drugs: Polatuzumab vedotin (Lyophilized)
Participants in the New Formulation (NF) Cohort (Arms G and H) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib: Percentage of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
From the study start up to the end of the study (up to approximately 84 months)
Primary outcome [2] 0 0
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
Timepoint [2] 0 0
From Month 37 to Month 84 (up to approximately 47 months)
Primary outcome [3] 0 0
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
Timepoint [3] 0 0
Baseline up to approximately Month 24
Primary outcome [4] 0 0
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
Timepoint [4] 0 0
Baseline up to approximately Month 24
Primary outcome [5] 0 0
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
Timepoint [5] 0 0
From Month 37 to Month 84 (up to approximately 47 months)
Primary outcome [6] 0 0
Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)
Timepoint [6] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Primary outcome [7] 0 0
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Timepoint [7] 0 0
6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Primary outcome [8] 0 0
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
Timepoint [8] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Primary outcome [9] 0 0
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
Timepoint [9] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Primary outcome [10] 0 0
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
Timepoint [10] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Primary outcome [11] 0 0
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
Timepoint [11] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Secondary outcome [1] 0 0
Phase II: Percentage of Participants With AEs
Timepoint [1] 0 0
From the study start up to the end of the study (up to approximately 84 months)
Secondary outcome [2] 0 0
Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
Timepoint [2] 0 0
Baseline to approximately Month 24
Secondary outcome [3] 0 0
Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
Timepoint [3] 0 0
Baseline to approximately Month 24
Secondary outcome [4] 0 0
Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
Timepoint [4] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [5] 0 0
Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Timepoint [5] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [6] 0 0
Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
Timepoint [6] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [7] 0 0
Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
Timepoint [7] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [8] 0 0
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
Timepoint [8] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [9] 0 0
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
Timepoint [9] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [10] 0 0
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
Timepoint [10] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [11] 0 0
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
Timepoint [11] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Secondary outcome [12] 0 0
Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
Timepoint [12] 0 0
Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
Secondary outcome [13] 0 0
DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC
Timepoint [13] 0 0
Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
Secondary outcome [14] 0 0
DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator
Timepoint [14] 0 0
From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
Secondary outcome [15] 0 0
DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC
Timepoint [15] 0 0
From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
Secondary outcome [16] 0 0
DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator
Timepoint [16] 0 0
From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
Secondary outcome [17] 0 0
DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC
Timepoint [17] 0 0
From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
Secondary outcome [18] 0 0
Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
Timepoint [18] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Secondary outcome [19] 0 0
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator
Timepoint [19] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Secondary outcome [20] 0 0
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
Timepoint [20] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Secondary outcome [21] 0 0
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator
Timepoint [21] 0 0
Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Secondary outcome [22] 0 0
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC
Timepoint [22] 0 0
Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Secondary outcome [23] 0 0
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator
Timepoint [23] 0 0
From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Secondary outcome [24] 0 0
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC
Timepoint [24] 0 0
From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Secondary outcome [25] 0 0
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator
Timepoint [25] 0 0
From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Secondary outcome [26] 0 0
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC
Timepoint [26] 0 0
From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Secondary outcome [27] 0 0
Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator
Timepoint [27] 0 0
From Month 37 to Month 84 (up to approximately 47 months)
Secondary outcome [28] 0 0
Phase II NF Cohorts: Overall Survival (OS)
Timepoint [28] 0 0
From Month 37 to Month 84 (up to approximately 47 months)
Secondary outcome [29] 0 0
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Timepoint [29] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Secondary outcome [30] 0 0
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
Timepoint [30] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Secondary outcome [31] 0 0
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
Timepoint [31] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Secondary outcome [32] 0 0
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
Timepoint [32] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Secondary outcome [33] 0 0
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
Timepoint [33] 0 0
6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Secondary outcome [34] 0 0
Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
Timepoint [34] 0 0
Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Secondary outcome [35] 0 0
Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
Timepoint [35] 0 0
Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Secondary outcome [36] 0 0
Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab
Timepoint [36] 0 0
Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)
Secondary outcome [37] 0 0
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab
Timepoint [37] 0 0
Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Secondary outcome [38] 0 0
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Timepoint [38] 0 0
Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Secondary outcome [39] 0 0
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Timepoint [39] 0 0
Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose
Secondary outcome [40] 0 0
Plasma Concentration of Bendamustine
Timepoint [40] 0 0
Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose
Secondary outcome [41] 0 0
Serum Concentration of Rituximab
Timepoint [41] 0 0
Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)
Secondary outcome [42] 0 0
Serum Concentration of Obinutuzumab
Timepoint [42] 0 0
Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Secondary outcome [43] 0 0
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
Timepoint [43] 0 0
Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [44] 0 0
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Timepoint [44] 0 0
Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [45] 0 0
Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
Timepoint [45] 0 0
Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [46] 0 0
Phase II: Cmax of Bendamustine and Rituximab in Arms B and D
Timepoint [46] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [47] 0 0
Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F
Timepoint [47] 0 0
Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [48] 0 0
Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)
Timepoint [48] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Secondary outcome [49] 0 0
Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
Timepoint [49] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [50] 0 0
Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Timepoint [50] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [51] 0 0
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
Timepoint [51] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [52] 0 0
Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D
Timepoint [52] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [53] 0 0
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F
Timepoint [53] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [54] 0 0
Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)
Timepoint [54] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Secondary outcome [55] 0 0
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
Timepoint [55] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [56] 0 0
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Timepoint [56] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [57] 0 0
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
Timepoint [57] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [58] 0 0
Phase II: CL of Bendamustine and Rituximab in Arms B and D
Timepoint [58] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [59] 0 0
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
Timepoint [59] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [60] 0 0
Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)
Timepoint [60] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Secondary outcome [61] 0 0
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a
Timepoint [61] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [62] 0 0
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Timepoint [62] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [63] 0 0
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
Timepoint [63] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [64] 0 0
Phase II: Vss of Bendamustine and Rituximab in Arms B and D
Timepoint [64] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [65] 0 0
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
Timepoint [65] 0 0
Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Secondary outcome [66] 0 0
Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)
Timepoint [66] 0 0
Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Secondary outcome [67] 0 0
Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F
Timepoint [67] 0 0
Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)

Eligibility
Key inclusion criteria
- Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or
refractory DLBCL

- If the participant has received prior bendamustine, response duration must have been
greater than (>) 1 year (for participants who have relapse disease after a prior
regimen)

- At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5
centimeters (cm) in its longest dimension

- Confirmed availability of archival or freshly collected tumor tissue

- The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology
report for central pathology review.

- Life expectancy of at least 24 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Adequate hematological function unless inadequate function is due to underlying
disease
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies (MAbs, or recombinant antibody-related fusion proteins) or known
sensitivity or allergy to murine products

- Contraindication to bendamustine, rituximab, or obinutuzumab

- Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4
weeks or 5 half-lives before Cycle 1 Day 1

- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy,
or any investigational agent for the purposes of treating cancer within 2 weeks prior
to Cycle 1 Day 1

- Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes other
than lymphoma symptom control

- Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1
Day 1

- Prior allogeneic SCT

- Eligibility for autologous SCT

- Grade 3b FL

- History of transformation of indolent disease to DLBCL

- Primary or secondary CNS lymphoma

- Current Grade >1 peripheral neuropathy

- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (such as New York Heart Association Class III or IV cardiac
disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
unstable angina) or significant pulmonary disease (including obstructive pulmonary
disease and history of bronchospasm)

- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment or any major episode of
infection requiring treatment with IV antibiotics or hospitalization within 4 weeks
prior to Cycle 1 Day 1

- Suspected or latent tuberculosis

- Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C
virus (HCV) antibody

- Known history of human immunodeficiency virus (HIV) seropositive status or known
infection with human T-cell leukemia virus 1 (HTLV-1) virus

- Women who are pregnant or lactating or who intend to become pregnant within a year of
the last dose of study treatment in the rituximab cohort or within 18 months of last
dose in the obinutuzumab cohort

- Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation
function tests

- Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle
1, Day 1

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/10/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/10/2021
Sample size
Target
Accrual to date
Final
331
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Prince of Wales Hospital; Oncology - Randwick
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [4] 0 0
Monash Medical Centre; Haematology Research - Clayton
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New Mexico
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Nova Scotia
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Czechia
State/province [18] 0 0
Brno
Country [19] 0 0
Czechia
State/province [19] 0 0
Hradec Kralove
Country [20] 0 0
Czechia
State/province [20] 0 0
Ostrava
Country [21] 0 0
Czechia
State/province [21] 0 0
Prague 2
Country [22] 0 0
France
State/province [22] 0 0
Dijon
Country [23] 0 0
France
State/province [23] 0 0
La Roche Sur Yon
Country [24] 0 0
France
State/province [24] 0 0
Lyon
Country [25] 0 0
France
State/province [25] 0 0
Montpellier
Country [26] 0 0
France
State/province [26] 0 0
Pierre Benite
Country [27] 0 0
France
State/province [27] 0 0
Rouen
Country [28] 0 0
Germany
State/province [28] 0 0
Erfurt
Country [29] 0 0
Germany
State/province [29] 0 0
Mainz
Country [30] 0 0
Germany
State/province [30] 0 0
Minden
Country [31] 0 0
Germany
State/province [31] 0 0
Münster
Country [32] 0 0
Germany
State/province [32] 0 0
Regensburg
Country [33] 0 0
Hungary
State/province [33] 0 0
Budapest
Country [34] 0 0
Hungary
State/province [34] 0 0
Debrecen
Country [35] 0 0
Italy
State/province [35] 0 0
Campania
Country [36] 0 0
Italy
State/province [36] 0 0
Lombardia
Country [37] 0 0
Italy
State/province [37] 0 0
Piemonte
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Netherlands
State/province [39] 0 0
Nijmegen
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Salamanca
Country [43] 0 0
Spain
State/province [43] 0 0
Sevilla
Country [44] 0 0
Turkey
State/province [44] 0 0
Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Izmir
Country [46] 0 0
Turkey
State/province [46] 0 0
Samsun
Country [47] 0 0
Turkey
State/province [47] 0 0
Trabzon
Country [48] 0 0
United Kingdom
State/province [48] 0 0
London
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Manchester
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Nottingham
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is a multicenter, open-label study of polatuzumab vedotin administered by
intravenous (IV) infusion in combination with standard doses of bendamustine (B) and
rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular
lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a
Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18
weeks for participants with DLBCL and 24 weeks for participants with FL.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02257567
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02257567