A Study of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus (+) Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Follicular Lymphoma (FL) or Rituximab + CHOP in Participants With Diffuse Large B-Cell Lymphoma (DLBCL)

NCT ID: NCT02596971

Last Updated: 2021-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-22
• Study Completion Date: 2020-05-08

Brief Summary

This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with either obinutuzumab + bendamustine (Atezo-G-benda) or obinutuzumab + CHOP (Atezo-G-CHOP) in participants with FL and atezolizumab + rituximab + chemotherapy (Atezo-R-CHOP) in participants with DLBCL, followed by post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in participants with FL who achieve a complete response (CR) or partial response (PR) at end of induction (EOI) or atezolizumab alone in participants with DLBCL who achieve a CR at EOI.

Conditions

Diffuse Large B-Cell Lymphoma, Lymphoma Follicular

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezo-G-Benda (Safety Run-In and Expansion Phases)

Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month \[q2m\]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL will receive same treatment regimen as described for safety run-in phase.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.

Bendamustine

Intervention Type: DRUG

Bendamustine will be administered at a dose of 90 milligrams per square meter (mg/m\^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment.

Obinutuzumab

Intervention Type: DRUG

Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.

Atezo-G-CHOP (Safety Run-In Phase)

Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide will be administered at a dose of 750 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be administered at a dose of 50 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Obinutuzumab

Intervention Type: DRUG

Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.

Prednisone

Intervention Type: DRUG

Prednisone will be administered at a dose of 40 mg/m\^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m\^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).

Vincristine

Intervention Type: DRUG

Vincristine will be administered at a dose of 1.4 mg/m\^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.

Atezo-R-CHOP (Expansion Phase)

Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide will be administered at a dose of 750 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be administered at a dose of 50 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Prednisone

Intervention Type: DRUG

Prednisone will be administered at a dose of 40 mg/m\^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m\^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).

Vincristine

Intervention Type: DRUG

Vincristine will be administered at a dose of 1.4 mg/m\^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.

Rituximab

Intervention Type: DRUG

Atezo-R-CHOP: Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m\^2 IV on Day 1 of Cycle 1-8, during induction treatment.

Interventions

Atezolizumab

Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.

Intervention Type: DRUG

Bendamustine

Bendamustine will be administered at a dose of 90 milligrams per square meter (mg/m\^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide will be administered at a dose of 750 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Intervention Type: DRUG

Doxorubicin

Doxorubicin will be administered at a dose of 50 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Intervention Type: DRUG

Obinutuzumab

Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.

Intervention Type: DRUG

Prednisone

Prednisone will be administered at a dose of 40 mg/m\^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m\^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).

Intervention Type: DRUG

Vincristine

Vincristine will be administered at a dose of 1.4 mg/m\^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.

Intervention Type: DRUG

Rituximab

Atezo-R-CHOP: Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m\^2 IV on Day 1 of Cycle 1-8, during induction treatment.

Intervention Type: DRUG

Other Intervention Names

RO5541267; Tecentriq; RO5072759

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment
• For participants enrolled in the expansion phase: lymphoma classified as either previously untreated Grade 1, 2, or 3a FL that requires treatment or previously untreated advanced DLBCL
• Histologically documented cluster of differentiation 20 (CD20) positive lymphoma
• Fluorodeoxyglucose-avid lymphoma
• At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
• Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
• For women who are not postmenopausal or surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than [<] 1 percent [%] per year during the treatment period and for at least 18 months after the last dose of study treatment for participants in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 12 months after the last dose of study treatment for participants in the Atezo-R-CHOP treatment group
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

Exclusion Criteria

• Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's lymphoma (NHL)
• Central nervous system lymphoma or leptomeningeal infiltration
• For participants with DLBCL: preplanned consolidative radiotherapy
• Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
• For participants with relapsed or refractory FL: prior allogeneic or autologous stem cell transplantation, anthracycline therapy, treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of Cycle 1, treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1, radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
• History of solid organ transplantation
• History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab, obinutuzumab, rituximab, or bendamustine formulation, including mannitol
• Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening
• History of progressive multifocal leukoencephalopathy
• Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1
• History of other malignancy, autoimmune disease, or any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results
• Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, or anticipation of a major surgical procedure during the course of the study
• For participants who will be receiving CHOP: left ventricular ejection fraction (LVEF) <50% by multiple-gated acquisition (MUGA) scan or echocardiogram
• Inadequate hematologic, renal, and liver function (unless due to underlying lymphoma)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University Miami

Miami, Florida, United States

New York Uni Medical Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Oncology Associates of Oregon, P.C.; Willamette Valley Cancer Institute

Springfield, Oregon, United States

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Texas Oncology

Austin, Texas, United States

Texas Oncology-Tyler

Irving, Texas, United States

Concord Repatriation General Hospital; Haematology

Sydney, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

The Queen Elizabeth Hospital; Haematology/Oncology

Woodville South, South Australia, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Azienda Ospedaliera S. Orsola-Malpighi

Bologna, Emilia-Romagna, Italy

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, Emilia-Romagna, Italy

Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia

Ravenna, Emilia-Romagna, Italy

Ospedale Infermi di Rimini

Rimini, Emilia-Romagna, Italy

AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette

Torino, Lazio, Italy

Asst Papa Giovanni XXIII

Bergamo, Lombardy, Italy

Azienda Ospedaliera Univ

Florence, Tuscany, Italy

Countries

United States; Australia; Italy

References

Younes A, Burke JM, Cheson BD, Diefenbach CS, Ferrari S, Hahn UH, Hawkes EA, Khan C, Lossos IS, Musuraca G, Tani M, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Sharman JP. Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma. Blood Adv. 2023 Apr 25;7(8):1488-1495. doi: 10.1182/bloodadvances.2022008344.

Reference Type: DERIVED

PMID: 36287231 (View on PubMed)

Younes A, Burke JM, Diefenbach C, Ferrari S, Khan C, Sharman JP, Tani M, Ujjani C, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Gilbertson M. Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. Blood Adv. 2022 Oct 25;6(20):5659-5667. doi: 10.1182/bloodadvances.2021006131.

Reference Type: DERIVED

PMID: 35359000 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-001364-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO29563

Identifier Type: -

Identifier Source: org_study_id