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A Study of Obinutuzumab, Polatuzumab Vedotin, and Atezolizumab in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02729896
First received: April 1, 2016
Last updated: December 21, 2016
Last verified: December 2016
  Purpose
This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab (G) + atezolizumab (Atezo) + polatuzumab vedotin (Pola) in participants with relapsed or refractory FL or DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for polatuzumab vedotin in this treatment combination, followed by an expansion phase in which polatuzumab vedotin will be given at the RP2D. All participants will receive induction treatment with G + 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) and DLBCL participants achieving a CR or PR at EOI will be eligible to receive post-induction treatment with obinutuzumab + atezolizumab.

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
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 OR 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:
  • Recommended Phase II Dose (RP2D) of Polatuzumab Vedotin in Combination With Fixed Doses of Obinutuzumab and Atezolizumab [ Time Frame: 6 months ]
  • Percentage of Participants with Adverse Events and Serious Adverse Events [ Time Frame: approximately 30 months ]
  • Percentage of Participants With Dose Limiting Toxicities (DLT) [ Time Frame: Day 1 Cycle 1 to Day 21 Cycle 2 (42 days) ]
  • Percentage of Participants With Complete Response (CR), 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 Complete Response (CR) at EOI, as Determined by Investigator 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) ]
  • Percentage of Participants With Complete Response (CR) at EOI, as Determined by IRC and Investigator on the Basis of CT Scan [ 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 Scan [ 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 Scan [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months) ]
  • Percentage of Participants With Best Overall Response, as Determined by the Investigator on the Basis of CT Scan [ Time Frame: approximately 30 months ]

Estimated Enrollment: 73
Study Start Date: May 2016
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (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 polatuzumab vedotin on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, atezolizumab on Day 1, and polatuzumab vedotin on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 and atezolizumab on Days 1 and 2 of each month for 24 months, during maintenance treatment for FL participants.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered intravenously (IV) at a flat dose of 840 milligram (mg) on Days 1 and 15 of Cycles 2 to 6, given in 21-day cycles during induction treatment, and on Days 1 and 2 every month during maintenance/consolidation treatment.
Drug: Obinutuzumab
Obinutuzumab will be administered IV at a flat does 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 second month (q2m) during maintenance/consolidation treatment.
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered IV at either 1.4 mg/kg or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose expansion phase) on Day 1 of Cycles 1-6, given in 21-day cycles during induction treatment.
Experimental: Expansion Phase
During the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and polatuzumab vedotin at identified RP2D (decided from dose escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, atezolizumab on Day 1, and polatuzumab vedotin at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 and atezolizumab on Days 1 and 2 of each month for 24 months (during maintenance treatment for FL participants) and for 8 months (during consolidation treatment for DLBCL participants).
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered intravenously (IV) at a flat dose of 840 milligram (mg) on Days 1 and 15 of Cycles 2 to 6, given in 21-day cycles during induction treatment, and on Days 1 and 2 every month during maintenance/consolidation treatment.
Drug: Obinutuzumab
Obinutuzumab will be administered IV at a flat does 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 second month (q2m) during maintenance/consolidation treatment.
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered IV at either 1.4 mg/kg or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose expansion phase) on Day 1 of Cycles 1-6, given in 21-day cycles during induction treatment.

  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) A21 Status of 0, 1, or 2
  • For participants enrolled in the dose-escalation phase: relapsed or refractory 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 participants enrolled in the expansion phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which not other more appropriate treatment option exists as determined by the investigator OR classified as Relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in patients who are not eligible for second line combination chemotherapy and autologous stem-cell transplantation or who have failed second line combination chemotherapy or experienced disease progression following autologous stem-cell transplantation
  • Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is positron emission tomography [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 <1% per year during the treatment period for >= 18 months after the 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 5 months after last dose of study drug, 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; central nervous system (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 months 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 cell death protein 1 (anti PD-1), anti programmed death-ligand 1 (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 > 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 less than (<) 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.rochegenentechtrials@roche.com

Locations
United States, Florida
University Miami Recruiting
Miami, Florida, United States, 33136
United States, New York
Stony Brook University Hospital Not yet 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 Not yet recruiting
Essen, Germany, 45122
Universitatsklinikum Frankfurt Not yet recruiting
Frankfurt, Germany, 60590
Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik Not yet recruiting
Greifswald, Germany, 17475
Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie Not yet recruiting
Hannover, Germany, 30625
Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie Not yet recruiting
Jena, Germany, 07747
Klinikum rechts der Isar der Technischen Universitat Munchen Not yet 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 Not yet 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 Not yet recruiting
Warsaw, Poland, 02-776
MTZ Clinical Research Sp. z o.o. Not yet recruiting
Warszawa, Poland, 02-106
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego Not yet 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: December 21, 2016

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
Antibodies, Monoclonal
Immunoconjugates
Obinutuzumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on March 28, 2017