Clinical Trials /

A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

NCT02611323

Description:

This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)
  • Official Title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GO29833
  • SECONDARY ID: 2015-001998-40
  • NCT ID: NCT02611323

Conditions

  • Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
ObinutuzumabDose-Escalation Cohort: FL
RituximabDose-Escalation Cohort: DLBCL
Polatuzumab VedotinDose-Escalation Cohort: FL
VenetoclaxDose-Escalation Cohort: FL

Purpose

This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.

Trial Arms

NameTypeDescriptionInterventions
Dose-Escalation Cohort: FLExperimentalParticipants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
  • Obinutuzumab
  • Polatuzumab Vedotin
  • Venetoclax
Dose-Escalation Cohort: DLBCLExperimentalParticipants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
  • Rituximab
  • Polatuzumab Vedotin
  • Venetoclax
Expansion Cohort: FLExperimentalParticipants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
  • Obinutuzumab
  • Polatuzumab Vedotin
  • Venetoclax
Expansion Cohort: DLBCLExperimentalParticipants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
  • Rituximab
  • Polatuzumab Vedotin
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

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

          -  For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or
             refractory FL after treatment with at least one prior chemoimmunotherapy regimen that
             included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody
             (mAb) and for which no other more appropriate treatment option exists, as determined
             by the investigator

          -  For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or
             refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen
             that included an anti-CD20 mAb and for which no curative option exists as determined
             by the investigator

          -  At least one bidimensionally measurable lesion

        Exclusion Criteria:

          -  Known CD20-negative status at relapse or progression

          -  Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days
             prior to Day 1 of Cycle 1

          -  Grade 3b FL

          -  History of transformation of indolent disease to DLBCL

          -  Current use of systemic corticosteroids greater than (>) 20 milligrams (mg) prednisone
             per day (or equivalent); or prior anti-cancer therapy to include: radioimmunoconjugate
             within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or
             radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2
             weeks prior to Day 1 of Cycle 1

          -  Central nervous system (CNS) disease

          -  Active infection

          -  Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for
             warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior
             to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star
             fruit within 3 days prior to first dose of venetoclax

          -  Positive for human immunodeficiency virus (HIV) or hepatitis B or C

          -  Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1

          -  Poor hematologic, renal, or hepatic function

          -  Pregnant or lactating women

          -  Life expectancy <3 months
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with CR, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with CR, Determined by the Investigator on the basis of PET and CT Scans
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with CR, Determined by the Investigator on the Basis of CT Scans Alone
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with CR, Determined by the IRC on the Basis of CT Scans Alone
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response, Determined by an IRC on the Basis of PET and CT Scans
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of PET and CT Scans
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response, Determined by an IRC on the Basis of CT Scans Alone
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days)
Safety Issue:
Description:
Measure:Percentage of Participants with Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
Time Frame:Baseline up to 5 years
Safety Issue:
Description:
Measure:Observed Serum Obinutuzumab Concentration
Time Frame:Pre-infusion (0 hour [hr]) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4, 6; Post-induction: pre-infusion (within 5 hr before dose) on Day 1 of Months 2, 8, 14, 20; at treatment discontinuation (up to Month 24), 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 1-2 days) (1 cycle: 21 days)
Measure:Observed Serum Rituximab Concentration
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 0.5 hr post-infusion on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycles 2, 4; pre-infusion (-5 hr), 0.5 hr post-infusion on Day 1 of Cycle 6 (infusion duration: 60-90 minutes) (1 cycle: 21 days)
Measure:Observed Serum Polatuzumab Vedotin Concentration
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycles 2, 4; Post-induction: at treatment discontinuation (up to Month 24); 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 90 minutes) (1 cycle: 21 days)
Measure:Observed Plasma Polatuzumab Vedotin Concentration
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; Cycle 1 Days 8, 15; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6 (infusion duration: 90 minutes) (1 cycle: 21 days)
Measure:Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycles 2, 4; Post-induction: at treatment discontinuation (up to Month 24); 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 90 minutes) (1 cycle: 21 days)
Measure:Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; Cycle 1 Days 8, 15; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6 (infusion duration: 90 minutes) (1 cycle: 21 days)
Measure:Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; Cycle 1 Days 8, 15; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6 (infusion duration: 90 minutes) (1 cycle: 21 days)
Measure:Observed Plasma Venetoclax Concentration
Time Frame:4 hr post-dose on Day 1 of Cycle 1 up to pre-dose (within 1 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: 4 hr post-dose on Day 1 of Cycle 1, pre-dose (within 1 hr prior to dose) and 2, 4, 6, and 8 hr post-dose on Day 1 of Cycle 2, pre-dose (within 1 hr prior to dose) on Day 1 of Cycles 4, and 6 (1 cycle: 21 days)
Measure:Percentage of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycle 6; Post-induction: at treatment discontinuation (up to Month 24), 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 1-2 days) (1 cycle: 21 days)
Measure:Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
Time Frame:Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description.
Safety Issue:
Description:Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycles 2, 4; Post-induction: at treatment discontinuation (up to Month 24), 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 1-2 days) (1 cycle: 21 days)
Measure:Recommended Phase 2 Dose (RP2D) of Polatuzumab Vedotin
Time Frame:Baseline up to 21 days
Safety Issue:
Description:
Measure:Recommended Phase 2 Dose (RP2D) of Venetoclax
Time Frame:Baseline up to 21 days
Safety Issue:
Description:
Measure:Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame:Baseline up to 21 days
Safety Issue:
Description:
Measure:Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Baseline up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

December 9, 2019