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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Obinutuzumab | | Dose-Escalation Cohort: FL |
| Rituximab | | Dose-Escalation Cohort: DLBCL |
| Polatuzumab Vedotin | | Dose-Escalation Cohort: DLBCL |
| Venetoclax | | Dose-Escalation Cohort: DLBCL |
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
| Name | Type | Description | Interventions |
|---|
| Dose-Escalation Cohort: FL | Experimental | Participants 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: DLBCL | Experimental | Participants 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: FL | Experimental | Participants 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: DLBCL | Experimental | Participants 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) |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
July 1, 2021
