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)

Roche

Status and phase: Completed; Phase 2; Phase 1

Conditions: Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Treatments: Drug: Polatuzumab Vedotin; Drug: Obinutuzumab; Drug: Lenalidomide; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02600897

GO29834

2015-001999-22 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 114 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 4 patient groups

Dose-escalation Cohort: FL

Experimental group

Description:

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).

Treatment:

Drug: Polatuzumab Vedotin

Drug: Obinutuzumab

Drug: Lenalidomide

Dose-escalation Cohort: DLBCL

Experimental group

Description:

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).

Treatment:

Drug: Rituximab

Drug: Polatuzumab Vedotin

Drug: Lenalidomide

Expansion Cohort: FL

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Lenalidomide

Expansion Cohort: DLBCL

Experimental group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Lenalidomide