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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)

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02729896
First received: April 1, 2016
Last updated: June 9, 2017
Last verified: June 2017
  Purpose
This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory FL and rituximab + Atezo + Pola in participants with relapsed or refractory 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. 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 + Atezo and DLBCL participants achieving a CR or PR at EOI will be eligible to receive consolidation treatment with rituximab + Atezo.

Condition Intervention Phase
Lymphoma Drug: Atezolizumab [TECENTRIQ] Drug: Obinutuzumab Drug: Polatuzumab Vedotin Drug: Rituximab Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants with CR at EOI, as Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) ]

Secondary Outcome Measures:
  • Percentage of Participants with CR at EOI, as Determined by Investigator on the Basis of PET-CT Scans [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) ]
  • Percentage of Participants with CR at EOI, as Determined by 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 6 months) ]
  • Percentage of Participants with Objective Response (CR + PR) at EOI, as Determined by the IRC and by the Investigator on the Basis of PET-CT Scans [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) ]
  • Percentage of Participants with Objective Response (CR + PR) at EOI, as Determined by the IRC and 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 6 months) ]
  • Percentage of Participants with Best Response of CR or PR during the Study, as Determined by the Investigator on the Basis of CT Scans Alone [ Time Frame: Baseline up to approximately 4 years ]
  • RP2D of Pola in Combination with Fixed Doses of Obinutuzumab and Atezo [ Time Frame: Cycle 1, 2 (21-day cycle) ]
  • Percentage of Participants with Adverse Events and Serious Adverse Events [ Time Frame: Baseline up to approximately 4 years ]
  • Percentage of Participants with Dose-Limiting Toxicities (DLT) [ Time Frame: Cycle 1, 2 (21-day cycle) ]
  • Serum Obinutuzumab Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr)

  • Serum Rituximab Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr)

  • Serum Atezo Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)

  • Serum Pola Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)

  • Plasma Pola Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; anytime on Days 8, 15 of Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6 up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)

  • Serum Pola Analyte Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)

  • Plasma Pola Analyte Concentration [ Time Frame: Pre-dose (0 hr) up to approximately 4 years ]
    pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; anytime on Days 8, 15 of Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6 up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)

  • Incidence of Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [ Time Frame: Baseline up to approximately 4 years ]
    Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)

  • Incidence of Human Anti-Chimeric Antibodies (HACAs) to Rituximab [ Time Frame: Baseline to approximately 4 years ]
    Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)

  • Incidence of Anti-Therapeutic Antibodies (ATAs) to Atezo [ Time Frame: Baseline to approximately 4 years ]
    Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)

  • Incidence of ATAs to Pola [ Time Frame: Baseline to approximately 4 years ]
    Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to approximately 4 years (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)


Estimated Enrollment: 92
Actual Study Start Date: November 9, 2016
Estimated Study Completion Date: March 31, 2022
Estimated Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 and Atezo on Days 1 and 2 of each month for 24 months, during maintenance treatment for FL participants.
Drug: 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, and 1680 mg every 4 weeks (Q4W; 840 mg Days 1 and 2 every month) during maintenance or consolidation treatment (1 cycle=21 days; infusion rate starts with 60 minutes (min) and decreases to 30 min).
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).
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).
Experimental: 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, Atezo 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 and Atezo on Days 1 and 2 of each month for 24 months (during maintenance treatment for FL participants).

For DLBCL, during consolidation treatment participants will receive rituximab on Day 1 of every other month starting with Month 1 and Atezo on Days 1 and 2 of each month for 8 months.

Drug: 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, and 1680 mg every 4 weeks (Q4W; 840 mg Days 1 and 2 every month) during maintenance or consolidation treatment (1 cycle=21 days; infusion rate starts with 60 minutes (min) and decreases to 30 min).
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).
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).
Drug: Rituximab
Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment and on Day 1 of every other month during consolidation treatment for DLBCL (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).
Experimental: Safety Run-In Phase
For DLBCL, during the induction treatment Cycle 1 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1. Cycles 2-6: participants will receive rituximab on Day 1, Atezo on Day 1, and Pola on Day 1.
Drug: 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, and 1680 mg every 4 weeks (Q4W; 840 mg Days 1 and 2 every month) during maintenance or consolidation treatment (1 cycle=21 days; infusion rate starts with 60 minutes (min) and decreases to 30 min).
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).
Drug: Rituximab
Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment and on Day 1 of every other month during consolidation treatment for DLBCL (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02729896

Contacts
Contact: Reference Study ID Number: BO29561 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, California
UCLA Withdrawn
Los Angeles, California, United States, 90095
United States, Florida
University Miami Recruiting
Miami, Florida, United States, 33136
United States, New York
Stony Brook University Hospital Recruiting
Stony Brook, New York, United States, 11794
United States, Washington
Columbia Basin Hem-Onc; Department Hematology Oncology Recruiting
Kennewick, Washington, United States, 99336
United States, West Virginia
Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology Recruiting
Morgantown, West Virginia, United States, 26506
Germany
Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin Recruiting
Dessau-Roßlau, Germany, 06847
Uniklinik Essen Recruiting
Essen, Germany, 45122
Universitatsklinikum Frankfurt Not yet recruiting
Frankfurt, Germany, 60590
Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik Recruiting
Greifswald, Germany, 17475
Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie Recruiting
Hannover, Germany, 30625
Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie Recruiting
Jena, Germany, 07747
Klinikum rechts der Isar der Technischen Universität München Recruiting
Munchen, Germany, 81675
Universitaetsklinikum Wuerzburg Recruiting
Wuerzburg, Germany, 97080
Poland
Szpitale Wojewodzkie w Gdyni Sp. z o.o. Recruiting
Gdynia, Poland, 81-519
Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego Recruiting
Lodz, Poland, 9351
Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW z W-MCO w Olsztynie Not yet recruiting
Olsztyn, Poland, 10-228
Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych Recruiting
Warsaw, Poland, 02-776
MTZ Clinical Research Sp. z o.o. Recruiting
Warszawa, Poland, 02-106
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego Recruiting
Warszawa, Poland, 02-781
Medical Uni of Wroclaw; Hematology Not yet recruiting
Wroclaw, Poland, 50-367
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02729896     History of Changes
Other Study ID Numbers: BO29561
2015-004845-25 ( EudraCT Number )
Study First Received: April 1, 2016
Last Updated: June 9, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Obinutuzumab
Rituximab
Antibodies, Monoclonal
Immunoconjugates
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on June 26, 2017