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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03677141
Other study ID # GO40515
Secondary ID 2018-001039-29
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date March 8, 2019
Est. completion date October 12, 2023

Study information

Verified date February 2024
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).


Recruitment information / eligibility

Status Completed
Enrollment 117
Est. completion date October 12, 2023
Est. primary completion date October 12, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria for Phase Ib and Phase II Portions - At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter - Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2 - Adequate hematologic function Inclusion Criteria for Phase Ib Portion Participants must also meet the following criteria for study entry into the Phase Ib portion: - Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen - Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy - Treatment with at least one prior CD20-directed therapy - Group B only: no prior treatment with polatuzumab vedotin Inclusion Criteria for Phase II Portion Participants must also meet the following criteria for study entry in the Phase II portion: - Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification - International Prognostic Index (IPI) score of 2-5 Exclusion Criteria - Prior treatment with mosunetuzumab - Prior allogenic stem-cell transplant - Current Grade >1 peripheral neuropathy - Participants with history of confirmed progressive multifocal leukoencephalopathy (PML) - Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV) - Prior solid organ transplantation - History of autoimmune disease - Current or past history of central nervous system (CNS) lymphoma - Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease - Significant cardiovascular disease or pulmonary disease - Clinically significant history of liver disease - Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis Exclusion Criteria for Phase Ib Portion Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion: - Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1 - Prior treatment with radiotherapy within 2 weeks prior to C1D1 - Adverse events from prior anti-cancer therapy resolved to =Grade 1 (with the exception of alopecia and anorexia) - Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose) Exclusion Criteria for Phase II Portion Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion: - Participants with transformed lymphoma - Prior therapy for B-cell NHL

Study Design


Intervention

Drug:
Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab.
Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV.
Rituxumab
Participants will receive rituxumab via IV.
Cyclophosphamide
Participants will receive cyclophosphamide via IV.
Doxorubicin
Participants will receive doxorubicin via IV.
Vincristine
Participants will receive vincristine via IV.
Prednisone
Participants will receive oral prednisone.
Tocilizumab
Participants will receive tocilizumab via IV.

Locations

Country Name City State
Austria Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU Salzburg
Austria LKH Steyr Steyr
Austria Hanusch-Krankenhaus Wien
Austria Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien Wien
France CHU Henri Mondor; Service d'Oncologie Medicale Creteil
France Centre Leon Berard Lyon
France Hôpital Saint-Louis Paris
France Centre Henri Becquerel- Centre de Lutte Contre le Cancer Saint Herblain
France Gustave Roussy Villejuif
Korea, Republic of Pusan National University Yangsan Hospital Gyeongsangnam-do
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Poland Maria Sklodowska-Curie Memorial Cancer Centre Gliwice
Poland Ma?opolskie Centrum Medyczne Kraków
Poland Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka Slupsk
Poland Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych Warsaw
Poland Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku Wroc?aw
Spain Institut Catala d?Oncologia Hospital Germans Trias i Pujol Badalona Barcelona
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Spain Hospital San Pedro de Alcantara; Servicio de Hematología Caceres
Spain Hospital General Universitario Gregorio Marañon Madrid
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital Universitario La Paz Madrid
Spain Clinica Universidad de Navarra Pamplona Navarra
Spain Hospital Universitario Virgen Macarena Seville Sevilla
United States University of Michigan Ann Arbor Michigan
United States University of Alabama Birmingham Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Banner MD Anderson Cancer Center Greeley Colorado
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States University of California; Moores Cancer Center La Jolla California
United States University of Miami Miller School of Medicine Miami Florida
United States Medical College of Wisconsin, Inc. Milwaukee Wisconsin
United States Vanderbilt University Medical Center Nashville Tennessee
United States Rhode Island Hospital Providence Rhode Island
United States Mayo Clinic Cancer Center Rochester Minnesota
United States University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica Santa Monica California
United States Scott and White Hospital; Cancer Center Temple Texas
United States Georgetown University Medical Center Washington District of Columbia
United States University of Kansas Cancer Center Westwood Kansas

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Austria,  France,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants with Adverse Events (AE) Baseline through approximately 90 days after the last study treatment
Primary Complete Response (CR) Rate at the Time of Primary Response Assessment Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Assessed According to Lugano 2014 Response Criteria Approximately 6-8 weeks after Cycle 6 (cycle = 21 days), or at early treatment discontinuation
Secondary Maximum Serum Concentration (Cmax) of Mosunetuzumab At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Minimum Serum Concentration (Cmin) of Mosunetuzumab At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Area Under the Curve (AUC) of Mosunetuzumab At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Clearance (CL) of Mosunetuzumab At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Volume of Distribution at Steady State (Vss) of Mosunetuzumab At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Maximum Plasma Concentration (Cmax) of Polatuzumab Vedotin At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Minimum Plasma Concentration (Cmin) of Polatuzumab Vedotin At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary AUC of Polatuzumab Vedotin At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary CL of Polatuzumab Vedotin At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Vss of Polatuzumab Vedotin At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Best Objective Response Rate (ORR), Defined as Complete Response (CR) or Partial Response (PR) at any Time on Study Based on PET-CT and/or CT scan as Assessed According to Lugano 2014 Response Criteria Baseline through 2 years after partial response assessment (PRA) (up to a total of approximately 2.5 years)
Secondary Duration of Response (DOR) From the first occurrence of a response to disease progression, relapse, or death, whichever comes first (up to approximately 2.5 years)
Secondary Anti-Drug Antibodies (ADAs) to Mosunetuzumab At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary ADAs to Polatuzumab Vedotin At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Secondary Progression-Free Survival (PFS) From randomization to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary PFS at 1 Year Randomization to 1 Year
Secondary Event-Free Survival (EFS) From randomization to the first occurrence of disease progression or relapse, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first (up to approximately 2.5 years)
Secondary Time to Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) Physical Functioning and Fatigue From baseline through follow-up (up to approximately 2.5 years)
Secondary Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale From baseline through follow-up (up to approximately 2.5 years)
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