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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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02257567
Collaborator
(none)
331
Enrollment
62
Locations
12
Arms
84.2
Actual Duration (Months)
5.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
331 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 :
Oct 15, 2014
Actual Primary Completion Date :
Oct 20, 2021
Actual Study Completion Date :
Oct 20, 2021

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Rituxan; MabThera

    • Drug: 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).
    Other Names:
  • 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 Names:
  • 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 Names:
  • Rituxan; MabThera

    • Drug: 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).
    Other Names:
  • DCDS4501S

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase Ib: Percentage of Participants with Adverse Events [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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]) [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) [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]) [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) [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) [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) [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) [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) [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) [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Up to 50 months]

    31. Phase II NF Cohorts: Overall Survival (OS) [Up to 50 months]

    32. Pharmacokinetics: Area Under Concentration-Time Curve (AUC) of Polatuzumab (lyophilized) in Arm H [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 [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 [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 [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 [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 [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 [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 [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 Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294-3300
    2 Clearview Cancer Institute Huntsville Alabama United States 35805
    3 City of Hope National Medical Center Duarte California United States 91010
    4 Univ of Colorado Canc Ctr Aurora Colorado United States 80045
    5 Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy) Jacksonville Florida United States 32256
    6 Emory Univ Winship Cancer Inst Atlanta Georgia United States 30322
    7 Joliet Oncology-Hematology; Associates, Ltd. Joliet Illinois United States 60435
    8 Horizon Oncology Research, Inc. Lafayette Indiana United States 47905
    9 Weinberg CA Inst Franklin Sq Baltimore Maryland United States 21237
    10 Regional Cancer Care Associates LLC - Morristown Morristown New Jersey United States 07962
    11 University of New Mexico Cancer Center Albuquerque New Mexico United States 87131
    12 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    13 Levine Cancer Institute Charlotte North Carolina United States 28204
    14 West Clinic Germantown Tennessee United States 38138
    15 Swedish Cancer Inst. Seattle Washington United States 98104
    16 Northwest Medical Specialties Tacoma Washington United States 98405
    17 Prince of Wales Hospital; Oncology Randwick New South Wales Australia 2031
    18 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    19 Adelaide Cancer Centre Kurralta Park South Australia Australia 5037
    20 Monash Medical Centre; Haematology Research Clayton Victoria Australia 3168
    21 BCCA-Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
    22 Queen Elizabeth II Health Sciences Centre; Oncology Halifax Nova Scotia Canada B3H 2Y9
    23 Hopital Maisonneuve- Rosemont; Oncology Montreal Quebec Canada H1T 2M4
    24 Jewish General Hospital Montreal Quebec Canada H3T 1E2
    25 Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika Brno Czechia 625 00
    26 Fakultni nemocnice Hradec Kralove Hradec Kralove Czechia 500 05
    27 Fakultní nemocnice Ostrava Klinika hematoonkologie Ostrava Czechia 70852
    28 I Interni klinika; Vseobecna fakultni nemocnice Prague 2 Czechia 128 08
    29 Chu Site Du Bocage;Hematologie Clinique Dijon France 21079
    30 Centre Hospitalier Departemental Les Oudairies La Roche Sur Yon France 85925
    31 Centre Leon Berard; Departement Oncologie Medicale Lyon France 69373
    32 CHU Saint Eloi; Service d'Hématologie Clinique Montpellier France 34295
    33 CHU Lyon Sud - Service Hématologie Pierre Benite France 69310
    34 Centre Henri Becquerel; Hematologie Rouen France 76038
    35 HELIOS Klinikum Erfurt - Innere Medizin - 4. Medizinische Klinik, Hämatologie Erfurt Germany 99089
    36 Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Abt. für Hämatologie und Onkologie Mainz Germany 55131
    37 Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Hämatologie, Onkologie und Pallia. Minden Germany 32429
    38 Gemeinschaftspraxis für Hämatologie und Onkologie Münster Germany 48153
    39 Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale Regensburg Germany 93053
    40 Semmelweis University, First Dept of Medicine Budapest Hungary 1083
    41 National Institute of Oncology, A Dept of Internal Medicine Budapest Hungary 1122
    42 University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B Debrecen Hungary 4032
    43 Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica Napoli Campania Italy 80131
    44 A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia Brescia Lombardia Italy 25123
    45 Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia Milano Lombardia Italy 20141
    46 Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia Alessandria Piemonte Italy 15121
    47 Seoul National University Hospital Seoul Korea, Republic of 03080
    48 Samsung Medical Center Seoul Korea, Republic of 06351
    49 UMC St. Radboud; Hematology Nijmegen Netherlands 6525 GA
    50 Hospital Universitari Vall d'Hebron; Servicio de Hematologia Barcelona Spain 08035
    51 Hospital Clinic i Provincial de Barcelona; Hematology Barcelona Spain 08036
    52 Hospital Universitario la Paz; Servicio de Hematologia Madrid Spain 28046
    53 Hospital Clinico Universitario de Salamanca;Servicio de Hematologia Salamanca Spain 37007
    54 Hospital Universitario Virgen del Rocio; Servicio de Hematologia Sevilla Spain 41013
    55 Ankara University; Hematology Ankara Turkey 06620
    56 Dokuz Eylul Uni ; Hematology Izmir Turkey 35100
    57 Ondokuzmayis University Medical Faculty Heamatology Department Samsun Turkey 55139
    58 Karadeniz Technical Uni School of Medicine; Hematology Trabzon Turkey 61800
    59 KING'S COLLEGE HOSPITAL; Commercial R&D Amendments, King's Health Partner's Clinical Trials Office London United Kingdom SE1 9RT
    60 Christie Hospital Nhs Trust; Medical Oncology Manchester United Kingdom M2O 4BX
    61 Nottingham City Hospital; Dept of Haematology Nottingham United Kingdom NG5 1PB
    62 Southampton General Hospital; Somers Cancer Research Building Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02257567
    Other Study ID Numbers:
    • GO29365
    • 2014-001361-28
    First Posted:
    Oct 6, 2014
    Last Update Posted:
    Dec 1, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Large B-Cell, Diffuse
    Rituximab
    Obinutuzumab
    Bendamustine Hydrochloride
    Antibodies, Monoclonal
    Immunoconjugates

    Study Results

    No Results Posted as of Dec 1, 2021