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)

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 23, 2022

Interventions

  • Drug: Lenalidomide
    • All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.
  • Drug: Obinutuzumab
    • Participants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by post-induction treatment at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months until disease progression or unacceptable toxicity.
  • Drug: Polatuzumab Vedotin
    • Participants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment.
  • Drug: Rituximab
    • Participants will receive a fixed dose of rituximab, 375 mg/m^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.

Arms, Groups and Cohorts

  • Experimental: Dose-escalation Cohort: FL
    • 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).
  • Experimental: Dose-escalation Cohort: DLBCL
    • 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).
  • Experimental: Expansion Cohort: FL
    • 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.
  • Experimental: Expansion Cohort: DLBCL
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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)
  • Percentage of Participants with Adverse Events (AEs)
    • Time Frame: Up to approximately 3 years
  • Percentage of Participants with Dose-Limiting Toxicities (DLTs)
    • Time Frame: Up to approximately 3 years

Secondary Measures

  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hoffmann-La Roche
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trials, Study Director, Hoffmann-La Roche

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