Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Participants With Previously Untreated Diffuse Large B-Cell Lymphoma

NCT ID: NCT03677154

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-23
• Study Completion Date: 2025-08-07

Brief Summary

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

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

Study Groups

Consolidation Therapy (Cohort A)

Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).

Group Type: EXPERIMENTAL

Mosunetuzumab Intravenous (IV)

Intervention Type: DRUG

Participants in cohorts A and B will receive IV mosunetuzumab.

Tocilizumab

Intervention Type: DRUG

Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).

Elderly/Unfit Previously Untreated Monotherapy (Cohort B)

Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).

Group Type: EXPERIMENTAL

Mosunetuzumab Intravenous (IV)

Intervention Type: DRUG

Participants in cohorts A and B will receive IV mosunetuzumab.

Tocilizumab

Intervention Type: DRUG

Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).

Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)

Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.

Group Type: EXPERIMENTAL

Mosunetuzumab Subcutaneous (SC)

Intervention Type: DRUG

Participants in Cohort C will receive SC mosunetuzumab.

Polatuzumab Vedotin

Intervention Type: DRUG

Participants in Cohort C will receive IV polatuzumab vedotin.

Tocilizumab

Intervention Type: DRUG

Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).

Interventions

Mosunetuzumab Intravenous (IV)

Participants in cohorts A and B will receive IV mosunetuzumab.

Intervention Type: DRUG

Mosunetuzumab Subcutaneous (SC)

Participants in Cohort C will receive SC mosunetuzumab.

Intervention Type: DRUG

Polatuzumab Vedotin

Participants in Cohort C will receive IV polatuzumab vedotin.

Intervention Type: DRUG

Tocilizumab

Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Adequate hematologic function
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; with the exception of South Korea, where participants 80 years or older with ECOG >/= 2 will not be eligible

Participants in Cohort A must also meet the following criteria for study entry:

• Histologically confirmed DLBCL according to World Health Organization (WHO) 2016 expected to express the cluster of differentiation-20 (CD20) antigen
• One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing regimen for previously untreated DLBCL
• Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction treatment in accordance with the Lugano 2014 criteria

Participants in Cohorts B and C must also meet the following criteria for study entry:

• Previously untreated, histologically confirmed, DLBCL according to WHO 2016 classification
• Age >/= 80 years, or
• Age 65-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least one of the following: Impairment in at least two activity of daily living (ADL) components as defined in the protocol; impairment in at least two instrumental ADL components as defined in the protocol; cumulative illness rating scale - geriactic (CIRS-G) score of at least one cormorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in >/= 8 comorbidities; impairment in cardiac function, renal function, liver function, or other comorbidities such that the participant is unfit for full-dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
• Participants with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase (not more than 100 mg/day up to 7 days prior to Cycle 1 Day 1) results in an improvement of ECOG performance status to </= 2 prior to enrollment

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from study entry:

• Transformed lymphoma
• CNS lymphoma
• Prior treatment with mosunetuzumab
• Prior stem cell transplant (autologous and allogeneic)
• 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)
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1
• Prior solid organ transplantation
• Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Clinically significant history of liver disease
• Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1)
• Significant cardiovascular disease

Participants in Cohort A who meet the following criteria will be excluded from study entry:

• Prior anti-lymphoma treatment with chemotherapy, immunotherapy, or biologic therapy 4 weeks prior to C1D1

Exclusion Criterion Specific to Cohorts B and C

Participants in Cohorts B and C who meet the following criterion will be excluded from study entry:

• Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy

Participants in Cohort C who meet the following criteria will be excluded from study entry:

• Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease

• 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

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, United States

University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica

Santa Monica, California, United States

Fort Wayne Medical Institute

Fort Wayne, Indiana, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Duke University

Durham, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Soroka Medical Center

Beersheba, , Israel

Rambam Medical Center

Haifa, , Israel

Carmel medical center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah Ein-Karem

Jerusalem, , Israel

Meir Medical Center

Kfar Saba, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

PRATIA MCM Kraków

Krakow, , Poland

Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli

Lublin, , Poland

Szpital Wojewodzki w Opolu

Opole, , Poland

Pusan National University Hospital

Busan, , South Korea

Keimyung University Dongsan Hospital

Daegu, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea Yeouido St. Mary's Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University

Seoul, , South Korea

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Hospital Universitario Vall d Hebron

Barcelona, , Spain

Institut Catala d Oncologia Hospitalet

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

National Taiwan University Hospital

Taipei, , Taiwan

Countries

United States; Israel; Poland; South Korea; Spain; Taiwan

Other Identifiers

GO40554

Identifier Type: -

Identifier Source: org_study_id