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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

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ClinicalTrials.gov Identifier: NCT02257567
Recruitment Status : Recruiting
First Posted : October 6, 2014
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: Bendamustine Drug: Obinutuzumab Drug: Polatuzumab vedotin (Liquid) Drug: Rituximab Drug: Polatuzumab vedotin (Lyophilized) Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 314 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 15, 2014
Estimated Primary Completion Date : January 2, 2020
Estimated Study Completion Date : July 12, 2021


Arm Intervention/treatment
Experimental: Arm A (Phase II Randomization): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: DCDS4501A

Drug: 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).
Other Name: Rituxan; MabThera

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: Rituxan; MabThera

Experimental: Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: DCDS4501A

Drug: 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).
Other Name: Rituxan; MabThera

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: Rituxan; MabThera

Experimental: Arm E (Phase II Expansion): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: GA101; Gazyva; Gazyvaro

Drug: 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).
Other Name: DCDS4501A

Experimental: Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: GA101; Gazyva; Gazyvaro

Drug: 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).
Other Name: DCDS4501A

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: DCDS4501A

Drug: 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).
Other Name: Rituxan; MabThera

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: DCDS4501A

Drug: 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).
Other Name: Rituxan; MabThera

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: GA101; Gazyva; Gazyvaro

Drug: 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).
Other Name: DCDS4501A

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: GA101; Gazyva; Gazyvaro

Drug: 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).
Other Name: DCDS4501A

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: Rituxan; MabThera

Drug: Polatuzumab vedotin (Lyophilized)
Participants in the New Formulation (NF) Cohort (Arm G) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F).
Other Name: DCDS4501S

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.
Drug: 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).
Other Name: Treanda; Ribomustin; Levact

Drug: 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).
Other Name: Rituxan; MabThera

Drug: Polatuzumab vedotin (Lyophilized)
Participants in the New Formulation (NF) Cohort (Arm G) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F).
Other Name: DCDS4501S




Primary Outcome Measures :
  1. Phase Ib: Percentage of Participants with Adverse Events [ Time Frame: From Baseline until up to 90 days after last dose (up to 36 weeks overall) ]
  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) [ Time Frame: 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) ]
  3. Pharmacokinetics: Area Under Concentration-Time Curve (AUC) of Polatuzumab (lyophilized) in Arm G [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  4. Pharmacokinetics: Maximum Concentration (Cmax) of Polatuzumab (lyophilized) in Arm G [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  5. Pharmacokinetics: Systemic Clearance (CL) of Polatuzumab (lyophilized) in Arm G [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  6. Pharmacokinetics: Steady-State Volume of Distribution (Vss) of Polatuzumab (lyophilized) in Arm G [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  7. Arm G (Phase II NF Cohort): Percentage of Participants with Adverse Events [ Time Frame: From Baseline up to 2 years ]
  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 [ Time Frame: 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 Measures :
  1. Percentage of Participants with CR According to Modified Lugano Criteria as Measured by PET/CT Scan and Determined by the Investigator [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  3. Percentage of Participants with CR According to Modified Lugano Criteria as Measured by CT Scan and Determined by IRC and Investigator [ Time Frame: 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) ]
  4. Percentage of Participants with CR or PR According to Modified Lugano Criteria as Measured by CT Scan and Determined by IRC and Investigator [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  6. Phase II: Percentage of Participants with Adverse Events [ Time Frame: From Baseline until up to 90 days after last dose (up to 36 weeks overall) ]
  7. Phase Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Polatuzumab in Cohort 1A [ Time Frame: 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) ]
  8. Phase Ib: Percentage of Participants with ADAs to Polatuzumab and Obinutuzumab in Cohort 1B [ Time Frame: 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) ]
  9. Phase II: Percentage of Participants with ADAs to Polatuzumab in Arms A and C [ Time Frame: 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) ]
  10. Phase II: Percentage of Participants with ADAs to Polatuzumab and Obinutuzumab in Arms E and F [ Time Frame: 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) ]
  11. Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Rituximab in Cohort 1A (milligrams per milliliter [mg/mL]) [ Time Frame: 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) ]
  12. Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Obinutuzumab in Cohort 1B (mg/mL) [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  13. Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Rituximab in Cohort 1A (hour * milligrams per milliliter [h*mg/mL]) [ Time Frame: 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) ]
  14. Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Obinutuzumab in Cohort 1B (h*mg/mL) [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  15. Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Rituximab in Arms A and C (mg/mL) [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  16. Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Rituximab in Arms A and C (h*mg/mL) [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  17. Pharmacokinetics: Cmax of Bendamustine and Rituximab in Arms B and D (mg/mL) [ Time Frame: 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) ]
  18. Pharmacokinetics: AUC of Bendamustine and Rituximab in Arms B and D (h*mg/mL) [ Time Frame: 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) ]
  19. Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Obinutuzumab in Arms E and F (mg/mL) [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  20. Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Obinutuzumab in Arms E and F (h*mg/mL) [ Time Frame: Day 1 up to 2 years (detailed timeframe is given in outcome description section) ]
    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)

  21. Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  29. Phase II NF Cohorts: Percentage of Participants with ADAs to Polatuzumab (lyophilized) in Arms G and H [ Time Frame: 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) ]
  30. Phase II NF Cohorts: Event-Free Survival (EFS) Based on PET-CT or CT only, as Determined by the Investigator [ Time Frame: Up to 50 months ]
  31. Phase II NF Cohorts: Overall Survival (OS) [ Time Frame: Up to 50 months ]
  32. Pharmacokinetics: Area Under Concentration-Time Curve (AUC) of Polatuzumab (lyophilized) in Arm H [ Time Frame: Day 1 up to 1 year (detailed timeframe is given in outcome description section) ]
    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

  33. Pharmacokinetics: Maximum Concentration (Cmax) of Polatuzumab (lyophilized) in Arm H [ Time Frame: Day 1 up to 1 year (detailed timeframe is given in outcome description section) ]
    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

  34. Pharmacokinetics: Systemic Clearance (CL) of Polatuzumab (lyophilized) in Arm H [ Time Frame: Day 1 up to 1 year (detailed timeframe is given in outcome description section) ]
    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

  35. Pharmacokinetics: Steady-State Volume of Distribution (Vss) of Polatuzumab (lyophilized) in Arm H [ Time Frame: Day 1 up to 1 year (detailed timeframe given in outcome description section) ]
    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

  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]
  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 [ Time Frame: 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257567


Contacts
Contact: Reference Study ID Number: GO29365 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 93 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02257567     History of Changes
Other Study ID Numbers: GO29365
2014-001361-28 ( EudraCT Number )
First Posted: October 6, 2014    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Obinutuzumab
Rituximab
Bendamustine Hydrochloride
Antibodies, Monoclonal
Immunoconjugates
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action