ANZCTR - Registration

Registration number

NCT02257567

Ethics application status

Date submitted

2/10/2014

Date registered

6/10/2014

Date last updated

13/09/2021

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]

2014-001361-28

Secondary ID [2]

GO29365

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Lymphoma

Condition category

Condition code

Cancer

Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Cancer

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Phase Ib: Percentage of Participants with Adverse Events

Timepoint [1]

From Baseline until up to 90 days after last dose (up to 36 weeks overall)

Primary outcome [2]

Phase II: Percentage of Participants with Complete Response (CR) According to Modified Lugano Criteria as Measured by Positron Emission Tomography (PET)/Computed Tomography (CT) Scan and Determined by Independent Review Committee (IRC)

Timepoint [2]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Primary outcome [3]

Pharmacokinetics: Area Under Concentration-Time Curve (AUC) of Polatuzumab (lyophilized) in Arm G - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; randomly during post-treatment period (up to 2 years overall)

Timepoint [3]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Primary outcome [4]

Pharmacokinetics: Maximum Concentration (Cmax) of Polatuzumab (lyophilized) in Arm G - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; randomly during post-treatment period (up to 2 years overall)

Timepoint [4]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Primary outcome [5]

Pharmacokinetics: Systemic Clearance (CL) of Polatuzumab (lyophilized) in Arm G - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; randomly during post-treatment period (up to 2 years overall)

Timepoint [5]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Primary outcome [6]

Pharmacokinetics: Steady-State Volume of Distribution (Vss) of Polatuzumab (lyophilized) in Arm G - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; randomly during post-treatment period (up to 2 years overall)

Timepoint [6]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Primary outcome [7]

Arm G (Phase II NF Cohort): Percentage of Participants with Adverse Events

Timepoint [7]

From Baseline up to 2 years

Primary outcome [8]

Arm H (Phase II NF Cohort): CR Rate According to Modified Lugano Criteria as Measured by PET-CT at the Time of Primary Response Assessment and Determined by IRC

Timepoint [8]

6-8 weeks after Cycle 6, Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [1]

Percentage of Participants with CR According to Modified Lugano Criteria as Measured by PET/CT Scan and Determined by the Investigator

Timepoint [1]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [2]

Percentage of Participants with CR or Partial Response (PR) According to Modified Lugano Criteria as Measured by PET/CT Scan and Determined by IRC and Investigator

Timepoint [2]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [3]

Percentage of Participants with CR According to Modified Lugano Criteria as Measured by CT Scan and Determined by IRC and Investigator

Timepoint [3]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [4]

Percentage of Participants with CR or PR According to Modified Lugano Criteria as Measured by CT Scan and Determined by IRC and Investigator

Timepoint [4]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [5]

Percentage of Participants by Best Objective Response (BOR) According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan only and Determined by the Investigator

Timepoint [5]

Baseline, Cycle 3 Day 15, 6-8 weeks after Cycle 6 Day 1 (cycle length: 21 or 28 days), then every 6 months until progression, withdrawal or study close (up to about 4.5 years overall)

Secondary outcome [6]

Phase II: Percentage of Participants with Adverse Events

Timepoint [6]

From Baseline until up to 90 days after last dose (up to 36 weeks overall)

Secondary outcome [7]

Phase Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Polatuzumab in Cohort 1A

Timepoint [7]

Pre-dose (0 to 4 hours [h]) on Day 2 of Cycle 1; pre-dose (0 to 4 h) on Day 1 of Cycles 2 and 4; randomly during post-treatment period (up to 2 years overall)

Secondary outcome [8]

Phase Ib: Percentage of Participants with ADAs to Polatuzumab and Obinutuzumab in Cohort 1B

Timepoint [8]

Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; pre-dose (0 to 4 h) on Day 2 of Cycle 1; randomly during post-treatment period (up to 2 years overall)

Secondary outcome [9]

Phase II: Percentage of Participants with ADAs to Polatuzumab in Arms A and C

Timepoint [9]

Pre-dose (0 to 4 h) on Day 1 of Cycles 2, 4; pre-dose (0 to 4 h) on Day 2 of Cycle 1; up to 30 days after last dose (approximately 28 weeks); randomly during post-treatment period (up to 2 years overall)

Secondary outcome [10]

Phase II: Percentage of Participants with ADAs to Polatuzumab and Obinutuzumab in Arms E and F

Timepoint [10]

Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; pre-dose (0 to 4 h) on Day 2 of Cycle 1; up to 30 days after last dose (approximately 28 weeks); randomly during post-treatment period (up to 2 years overall)

Secondary outcome [11]

Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Rituximab in Cohort 1A (milligrams per milliliter [mg/mL])

Timepoint [11]

Predose (0 to 4 h), end of infusion (EOI) (Duration of infusion: 90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Day 2, Cycle 1 and Day 1 of Cycles 2,4; Days 8,15 of Cycle 1; randomly during post-treatment period (up to 2 years overall)

Secondary outcome [12]

Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Obinutuzumab in Cohort 1B (mg/mL) - Detailed timeframe: Pre-dose (0 to 4 h) on Day 1 of Cycle 1, 2, 4 and Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; at EOI (Duration of infusion: 90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; randomly during post-treatment period (up to 2 years overall)

Timepoint [12]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Secondary outcome [13]

Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Rituximab in Cohort 1A (hour * milligrams per milliliter [h*mg/mL])

Timepoint [13]

Pre-dose (0 to 4 h) and EOI (Duration of infusion:90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; on Days 8, 15 of Cycle 1; randomly during post-treatment period (up to 2 years overall)

Secondary outcome [14]

Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Obinutuzumab in Cohort 1B (h*mg/mL) - Detailed timeframe: Pre-dose (0 to 4 h) on Day 1 of Cycle 1, 2, 4 and Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; at EOI (Duration of infusion: 90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; randomly during post-treatment period (up to 2 years overall)

Timepoint [14]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Secondary outcome [15]

Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Rituximab in Arms A and C (mg/mL) - Detailed timeframe: Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; at EOI (Duration of infusion:90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)

Timepoint [15]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Secondary outcome [16]

Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Rituximab in Arms A and C (h*mg/mL) - Detailed timeframe: Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; at EOI (Duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)

Timepoint [16]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Secondary outcome [17]

Pharmacokinetics: Cmax of Bendamustine and Rituximab in Arms B and D (mg/mL)

Timepoint [17]

Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI (Duration of infusion:90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Days 1, 2 of Cycle 1; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1 (up to 3 months overall)

Secondary outcome [18]

Pharmacokinetics: AUC of Bendamustine and Rituximab in Arms B and D (h*mg/mL)

Timepoint [18]

Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI (Duration of infusion:90 minutes [1st infusion], 30 minutes [subsequent infusions]) on Days 1, 2 of Cycle 1; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1 (up to 3 months overall)

Secondary outcome [19]

Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Obinutuzumab in Arms E and F (mg/mL) - Detailed timeframe: Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI (Duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)

Timepoint [19]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Secondary outcome [20]

Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Obinutuzumab in Arms E and F (h*mg/mL) - Detailed timeframe: Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI (Duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)

Timepoint [20]

Day 1 up to 2 years (detailed timeframe is given in outcome description section)

Secondary outcome [21]

Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F

Timepoint [21]

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)

Secondary outcome [22]

Phase II NF Cohort: Duration of Response (DOR) According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan and Determined by the Investigator and IRC

Timepoint [22]

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 about 4.5 years overall)

Secondary outcome [23]

Phase II NF Cohort: Progression Free Survival (PFS) According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan and Determined by the Investigator and IRC

Timepoint [23]

From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to about 4.5 years overall)

Secondary outcome [24]

Phase II NF Cohort: Percentage of Participants with CR According to Modified Lugano Criteria as Measured by PET/CT Scan and Determined by the Investigator

Timepoint [24]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [25]

Phase II NF Cohort: Percentage of Participants with CR or PR According to Modified Lugano Criteria as Measured by PET/CT Scan and Determined by the Investigator and IRC

Timepoint [25]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [26]

Phase II NF Cohort (Arm G): Percentage of Participants with CR According to Modified Lugano Criteria as Measured by CT Scan only and Determined by the Investigator and IRC

Timepoint [26]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [27]

Phase II NF Cohort (Arm G): Percentage of Participants with CR or PR According to Modified Lugano Criteria as Measured by CT Scan only and Determined by the Investigator and IRC

Timepoint [27]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)

Secondary outcome [28]

Phase II NF Cohorts: Percentage of Participants by BOR According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan only and Determined by the Investigator and IRC

Timepoint [28]

Baseline, Cycle 3 Day 15, 6-8 weeks after Cycle 6 Day 1 (cycle length: 21 or 28 days), then every 6 months until progression, withdrawal or study close (up to about 4.5 years overall)

Secondary outcome [29]

Phase II NF Cohorts: Percentage of Participants with ADAs to Polatuzumab (lyophilized) in Arms G and H

Timepoint [29]

Pre-dose Cycle 1 Day 2, Cycle 2 Day 1, Cycle 4 Day 1; 30 days after last infusion Cycle 6 Day 1; randomly during post-treatment period (up to 2 years overall)

Secondary outcome [30]

Phase II NF Cohorts: Event-Free Survival (EFS) Based on PET-CT or CT only, as Determined by the Investigator

Timepoint [30]

Up to 50 months

Secondary outcome [31]

Phase II NF Cohorts: Overall Survival (OS)

Timepoint [31]

Up to 50 months

Secondary outcome [32]

Pharmacokinetics: Area Under Concentration-Time Curve (AUC) of Polatuzumab (lyophilized) in Arm H - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; during follow up at Month 3

Timepoint [32]

Day 1 up to 1 year (detailed timeframe is given in outcome description section)

Secondary outcome [33]

Pharmacokinetics: Maximum Concentration (Cmax) of Polatuzumab (lyophilized) in Arm H - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; during follow up at Month 3

Timepoint [33]

Day 1 up to 1 year (detailed timeframe is given in outcome description section)

Secondary outcome [34]

Pharmacokinetics: Systemic Clearance (CL) of Polatuzumab (lyophilized) in Arm H - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; during follow up at Month 3

Timepoint [34]

Day 1 up to 1 year (detailed timeframe is given in outcome description section)

Secondary outcome [35]

Pharmacokinetics: Steady-State Volume of Distribution (Vss) of Polatuzumab (lyophilized) in Arm H - Detailed time frame: Pre and post-dose on Cycle 1 Day 2, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1; 6 days after Day 2 infusion Cycle 1 Day 8; 13 days after Day 2 infusion Cycle 1 Day 15; 7 days after Day 2 infusion Cycle 3 Day 8; 14 days after Day 2 infusion Cycle 3 Day 15; 30 days after last infusion Cycle 6 Day 1; during follow-up at Month 3

Timepoint [35]

Day 1 up to 1 year (detailed timeframe given in outcome description section)

Secondary outcome [36]

DLBCL Cohorts: Percentage of Participants by Best Objective Response (BOR) According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan Only and Determined by IRC

Timepoint [36]

Baseline, Cycle 3 Day 15, 6-8 weeks after Cycle 6 Day 1 (cycle length: 21 or 28 days), then every 6 months until progression, withdrawal or study close (up to about 4.5 years overall)

Secondary outcome [37]

DLBCL Cohorts: Duration of Response (DOR) According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan and Determined by IRC

Timepoint [37]

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 about 4.5 years overall)

Secondary outcome [38]

DLBCL Cohorts: Progression Free Survival (PFS) According to Modified Lugano Criteria as Measured by PET/CT Scan or CT Scan and Determined by IRC

Timepoint [38]

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 about 4.5 years overall)

Secondary outcome [39]

Phase II NF Cohort (Arm G): Percentage of Participants with CR According to Modified Lugano Criteria as Measured by PET/CT Scan and Determined by IRC

Timepoint [39]

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks 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

Gender

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

Statistical methods / analysis

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

Actual

15/10/2014

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

30/10/2021

Actual

Sample size

Target

Accrual to date

Final

331

Recruitment in Australia

Recruitment state(s)

NSW,SA,VIC

Recruitment hospital [1]

Prince of Wales Hospital; Oncology - Randwick

Recruitment hospital [2]

Royal Adelaide Hospital - Adelaide

Recruitment hospital [3]

Adelaide Cancer Centre - Kurralta Park

Recruitment hospital [4]

Monash Medical Centre; Haematology Research - Clayton

Recruitment postcode(s) [1]

2031 - Randwick

Recruitment postcode(s) [2]

5000 - Adelaide

Recruitment postcode(s) [3]

5037 - Kurralta Park

Recruitment postcode(s) [4]

3168 - Clayton

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Alabama

Country [2]

United States of America

State/province [2]

California

Country [3]

United States of America

State/province [3]

Colorado

Country [4]

United States of America

State/province [4]

Florida

Country [5]

United States of America

State/province [5]

Georgia

Country [6]

United States of America

State/province [6]

Illinois

Country [7]

United States of America

State/province [7]

Indiana

Country [8]

United States of America

State/province [8]

Maryland

Country [9]

United States of America

State/province [9]

New Jersey

Country [10]

United States of America

State/province [10]

New Mexico

Country [11]

United States of America

State/province [11]

New York

Country [12]

United States of America

State/province [12]

North Carolina

Country [13]

United States of America

State/province [13]

Tennessee

Country [14]

United States of America

State/province [14]

Washington

Country [15]

Canada

State/province [15]

British Columbia

Country [16]

Canada

State/province [16]

Nova Scotia

Country [17]

Canada

State/province [17]

Quebec

Country [18]

Czechia

State/province [18]

Brno

Country [19]

Czechia

State/province [19]

Hradec Kralove

Country [20]

Czechia

State/province [20]

Ostrava

Country [21]

Czechia

State/province [21]

Prague 2

Country [22]

France

State/province [22]

Dijon

Country [23]

France

State/province [23]

La Roche Sur Yon

Country [24]

France

State/province [24]

Lyon

Country [25]

France

State/province [25]

Montpellier

Country [26]

France

State/province [26]

Pierre Benite

Country [27]

France

State/province [27]

Rouen

Country [28]

Germany

State/province [28]

Erfurt

Country [29]

Germany

State/province [29]

Mainz

Country [30]

Germany

State/province [30]

Minden

Country [31]

Germany

State/province [31]

Münster

Country [32]

Germany

State/province [32]

Regensburg

Country [33]

Hungary

State/province [33]

Budapest

Country [34]

Hungary

State/province [34]

Debrecen

Country [35]

Italy

State/province [35]

Campania

Country [36]

Italy

State/province [36]

Lombardia

Country [37]

Italy

State/province [37]

Piemonte

Country [38]

Korea, Republic of

State/province [38]

Seoul

Country [39]

Netherlands

State/province [39]

Nijmegen

Country [40]

Spain

State/province [40]

Barcelona

Country [41]

Spain

State/province [41]

Madrid

Country [42]

Spain

State/province [42]

Salamanca

Country [43]

Spain

State/province [43]

Sevilla

Country [44]

Turkey

State/province [44]

Ankara

Country [45]

Turkey

State/province [45]

Izmir

Country [46]

Turkey

State/province [46]

Samsun

Country [47]

Turkey

State/province [47]

Trabzon

Country [48]

United Kingdom

State/province [48]

London

Country [49]

United Kingdom

State/province [49]

Manchester

Country [50]

United Kingdom

State/province [50]

Nottingham

Country [51]

United Kingdom

State/province [51]

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/show/NCT02257567

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Clinical Trials

Address

Hoffmann-La Roche

Country

Phone

Fax

Email

Contact person for public queries

Name

Address

Country

Phone

Fax

Email

Contact person for scientific queries

Summary results

Trial Review

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