Description:
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment
with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or
refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab
vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL),
followed by post-induction treatment with obinutuzumab in combination with lenalidomide in
participants with FL who achieve a complete response (CR), partial response (PR), or stable
disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus
lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.
Title
- Brief Title: A Study of Obinutuzumab, Polatuzumab Vedotin, and Lenalidomide in Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Relapsed or Refractory 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 Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
GO29834
- SECONDARY ID:
2015-001999-22
- NCT ID:
NCT02600897
Conditions
- Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Lenalidomide | | Dose-escalation Cohort: DLBCL |
Obinutuzumab | | Dose-escalation Cohort: FL |
Polatuzumab Vedotin | | Dose-escalation Cohort: DLBCL |
Rituximab | | Dose-escalation Cohort: DLBCL |
Purpose
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment
with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or
refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab
vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL),
followed by post-induction treatment with obinutuzumab in combination with lenalidomide in
participants with FL who achieve a complete response (CR), partial response (PR), or stable
disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus
lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose-escalation Cohort: FL | Experimental | Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle). | - Lenalidomide
- Obinutuzumab
- Polatuzumab Vedotin
|
Dose-escalation Cohort: DLBCL | Experimental | Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle). | - Lenalidomide
- Polatuzumab Vedotin
- Rituximab
|
Expansion Cohort: FL | Experimental | Participants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1. | |
Expansion Cohort: DLBCL | Experimental | Participants with R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1. | |
Eligibility Criteria
Inclusion Criteria:
- Age greater than or equal to (>/=) 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola +
Len) treatment group: R/R FL after treatment with at least one prior
chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for
which no other more appropriate treatment option exists as determined by the
investigator
- For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola +
Len) treatment group: R/R DLBCL after treatment with at least one prior
chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients
who are not eligible for autologous stem-cell transplantation or who have experienced
disease progression following treatment with high-dose chemotherapy plus autologous
stem-cell transplantation
- Histologically documented CD20-positive B-cell lymphoma as determined by the local
laboratory
- fluorodeoxyglucose (FDG)-avid lymphoma (i.e., positron emission tomography
(PET)-positive lymphoma)
- At least one bi-dimensionally measurable lesion
- Agreement to remain abstinent or use adequate contraception, among women or men of
childbearing potential
Exclusion Criteria:
- Grade 3b follicular lymphoma
- History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
- Known CD20-negative status at relapse or progression
- Central nervous system (CNS) lymphoma or leptomeningeal infiltration
- Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days
prior to Day 1 of Cycle 1
- Current use of systemic immunosuppressant(s), or prior anti-cancer therapy to include:
lenalidomide, fludarabine, or alemtuzumab within 12 months; 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
- Active infection
- 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 less than (<) 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 28 weeks) |
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 28 weeks) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with CR, Determined by the Independent Review Committee (IRC) and Investigator on the Basis of CT Scans Alone |
Time Frame: | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Objective Response, Determined by the IRC and 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 28 weeks) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Objective Response, Determined by the IRC and Investigator on the Basis of CT Scans Alone |
Time Frame: | Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) |
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 28 weeks) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With Best Response of Clinical Response (CR) or Partial Response (PR), Determined by the Investigator on the Basis of CT Scans Alone |
Time Frame: | Up to approximately 3 years |
Safety Issue: | |
Description: | |
Measure: | Observed Serum Obinutuzumab Concentration |
Time Frame: | Pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 1, 2, 4, and 6 during induction; pre-dose on Day 1 of Months 1, 7, 13, and/or 19 during the post-induction phase; then up to 2 years after last dose as available (maximum 5 years) |
Safety Issue: | |
Description: | |
Measure: | Observed Serum Rituximab Concentration |
Time Frame: | Pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 1, 2, 4, and 6 during induction; pre-dose on Day 1 of Months 1, 7, 13, and/or 19 during the post-induction phase; then up to 2 years after last dose as available (maximum 5 years) |
Safety Issue: | |
Description: | |
Measure: | Observed Serum and Plasma Polatuzumab Vedotin Concentration |
Time Frame: | Pre-dose and/or 30 minutes post-dose on Days 1, 8, and 15 of Cycle 1; pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 2, 4, and 6 during induction; then up to 2 years after last dose as available (maximum 5 years) |
Safety Issue: | |
Description: | |
Measure: | Observed Plasma Lenalidomide Concentration |
Time Frame: | Pre-dose and/or 0.5, 1, 2, 4, and 8 hours post-dose on Days 1 and 15 of Cycle 1 and on Day 1 of Cycle 6 (maximum 5 years) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab |
Time Frame: | Pre-dose on Day 1 of Cycles 1 and 6 during induction; then up to 2 years after last dose as available (maximum 5 years) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab |
Time Frame: | Pre-dose on Day 1 of Cycles 1 and 6 during induction; then up to 2 years after last dose as available (maximum 5 years) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin |
Time Frame: | Pre-dose on Day 1 of Cycles 1, 2, and 4 during induction; then up to 2 years after last dose as available (maximum 5 years) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 9, 2021