A Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

NCT ID: NCT02729896

Last Updated: 2020-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-09
• Study Completion Date: 2019-10-07

Brief Summary

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory (RR) FL and rituximab + Atezo + Pola in participants with RR DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for Pola in this treatment combination, followed by an expansion phase in which Pola will be given at the RP2D. All participants will receive induction treatment with obinutuzumab + Atezo + Pola for 6 cycles. RR FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) will receive maintenance treatment with obinutuzumab.

Conditions

Lymphoma

Study Design

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

Study Groups

Dose-Escalation Phase

During the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, Atezo on Day 1, and Pola on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants.

Group Type: EXPERIMENTAL

Atezolizumab [TECENTRIQ]

Intervention Type: DRUG

Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment.

NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).

Polatuzumab Vedotin

Intervention Type: DRUG

Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).

Expansion Phase

For FL during the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola at identified RP2D (decided from dose-escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1 and Pola at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months (during maintenance treatment for FL participants).

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).

Polatuzumab Vedotin

Intervention Type: DRUG

Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).

Rituximab

Intervention Type: DRUG

Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).

Safety Run-In Phase

For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1.

Group Type: EXPERIMENTAL

Atezolizumab [TECENTRIQ]

Intervention Type: DRUG

Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment.

NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.

Polatuzumab Vedotin

Intervention Type: DRUG

Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).

Rituximab

Intervention Type: DRUG

Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).

Interventions

Atezolizumab [TECENTRIQ]

Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment.

NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.

Intervention Type: DRUG

Obinutuzumab

Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).

Intervention Type: DRUG

Polatuzumab Vedotin

Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).

Intervention Type: DRUG

Rituximab

Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
• For rituximab + Atezo + Pola treatment group: relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in participants who are not eligible for second line combination (immuno-) chemotherapy and autologous stem-cell transplantation or who have failed second line combination (immuno-) chemotherapy or experienced disease progression following autologous stem-cell transplantation
• Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion
• 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 or to use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period for greater than or equal to (>=) 5 months after last dose of Atezo, >= 12 months after last dose of rituximab, >= 12 months after last dose of Pola, and >= 18 months after last dose of obinutuzumab
• For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of <1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab, rituximab, and Atezo and for 5 months after last dose of Pola, and agreement to refrain from donating sperm during this same period

Exclusion Criteria

• Grade 3b follicular lymphoma
• History of transformation of indolent disease to DLBCL
• Known CD20-negative status at relapse or progression; CNS lymphoma or leptomeningeal infiltration
• Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1)
• Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
• 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 D1C1
• History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies
• Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease
• Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1
• Pre-existing Grade greater than (>) 1 neuropathy
• Major surgical procedure other than for diagnosis within 28 days prior to D1C1
• Inadequate hematologic function, renal function, and liver function
• Pregnant or lactating women
• Life expectancy < 3 months

• 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

UCLA

Los Angeles, California, United States

University Miami

Miami, Florida, United States

Stony Brook University Hospital

Stony Brook, New York, United States

Columbia Basin Hem-Onc; Department Hematology Oncology

Kennewick, Washington, United States

Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology

Morgantown, West Virginia, United States

Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin

Dessau, , Germany

Uniklinik Essen

Essen, , Germany

Universitatsklinikum Frankfurt

Frankfurt, , Germany

Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik

Greifswald, , Germany

Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

Hanover, , Germany

Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie

Jena, , Germany

Klinikum rechts der Isar der Technischen Universität München

München, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Szpitale Wojewodzkie w Gdyni Sp. z o.o.

Gdynia, , Poland

Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego

Lodz, , Poland

MTZ Clinical Research Sp. z o.o.

Warsaw, , Poland

Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych

Warsaw, , Poland

Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego

Warsaw, , Poland

Medical Uni of Wroclaw; Hematology

Wroclaw, , Poland

Countries

United States; Germany; Poland

References

Topp MS, Eradat H, Florschutz A, Hochhaus A, Wrobel T, Walewski J, Knopinska-Posluszny W, Kanate AS, Lech-Maranda E, Brunnberg U, Chitra S, Nielsen TG, Sellam G, Shivhare M, Lossos IS. Anti-CD20-atezolizumab-polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma. J Cancer Res Clin Oncol. 2023 Feb;149(2):811-817. doi: 10.1007/s00432-021-03847-5. Epub 2022 Feb 18.

Reference Type: DERIVED

PMID: 35182224 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-004845-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO29561

Identifier Type: -

Identifier Source: org_study_id