A Phase III Study Evaluating Glofitamab in Combination With Gemcitabine + Oxaliplatin vs Rituximab in Combination With Gemcitabine + Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT ID: NCT04408638

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-23

Study Completion Date

2028-03-31

Brief Summary

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This study will evaluate the efficacy and safety of glofitamab in combination with gemcitabine plus oxaliplatin (Glofit-GemOx) compared with rituximab in combination with gemcitabine plus oxaliplatin (R-GemOx) in patients with R/R DLBCL.

Detailed Description

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Conditions

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Diffuse Large B-cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Glofit-GemOx

Participants will receive up to 8 cycles of glofitamab (Glofit) in combination with gemcitabine and oxaliplatin (GemOx), followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab. Treatment is administered in 21-day cycles.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.

Glofitamab

Intervention Type DRUG

Participants will receive IV glofitamab for up to 12 cycles.

Tocilizumab

Intervention Type DRUG

Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).

Gemcitabine

Intervention Type DRUG

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Oxaliplatin

Intervention Type DRUG

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

R-GemOx

Participants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.

Group Type EXPERIMENTAL

Rituxumab

Intervention Type DRUG

Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.

Gemcitabine

Intervention Type DRUG

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Oxaliplatin

Intervention Type DRUG

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Interventions

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Obinutuzumab

Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.

Intervention Type DRUG

Glofitamab

Participants will receive IV glofitamab for up to 12 cycles.

Intervention Type DRUG

Rituxumab

Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.

Intervention Type DRUG

Tocilizumab

Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).

Intervention Type DRUG

Gemcitabine

Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Intervention Type DRUG

Oxaliplatin

Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed diffuse large B-cell lymphoma (DLBCL), not otherwise specified
* Relapsed/refractory (R/R) disease, defined as follows: Relapsed = disease that has recurred ≥6 months after completion of the last line of therapy; Refractory = disease that either progressed during the last line of therapy or progressed within 6 months (\<6 months) of the last line of prior therapy
* At least one (≥1) line of prior systemic therapy
* Participants who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant, as defined by the study protocol
* Confirmed availability of tumor tissue, unless unobtainable per investigator assessment. Freshly collected biopsy is preferred. Archival tissue is acceptable
* At least one bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on computed tomography (CT) scan
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Adequate hematologic function (unless attributable to the underlying disease, as established by extensive bone marrow involvement or associated with hypersplenism secondary to the involvement of the spleen by DLBCL per the investigator), as defined by the study protocol
* Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
* Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min

Exclusion Criteria

* Patient has failed only one prior line of therapy and is a candidate for stem cell transplantation
* History of transformation of indolent disease to DLBCL
* High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma not otherwise specified, as defined by 2016 WHO guidelines
* Primary mediastinal B-cell lymphoma
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
* Contraindication to obinutuzumab, rituximab, gemcitabine or oxaliplatin, or tocilizumab
* Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
* Peripheral neuropathy assessed to be Grade \>1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
* Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
* Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
* Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
* Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
* Positive SARS-CoV-2 infection within 30 days prior to the first study treatment, including asymptomatic SARS-CoV-2 infection
* Documented SARS-CoV-2 infection within 6 months of first study treatment
* Suspected or latent tuberculosis
* Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
* Known or suspected chronic active Epstein-Barr viral infection
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
* Known history of progressive multifocal leukoencephalopathy
* Adverse events from prior anti-cancer therapy not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
* Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
* Prior solid organ transplantation
* Prior allogeneic stem cell transplant
* Active autoimmune disease requiring treatment
* Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
* Corticosteroid therapy within 2 weeks prior to first dose of study treatment (exceptions defined by study protocol)
* Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
* Clinically significant history of cirrhotic liver disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Community Cancer Institute (CCI)

Fresno, California, United States

Site Status

Baptist - MD Anderson Cancer Center

Jacksonville, Florida, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Monash Health Monash Medical Centre

Clayton, Victoria, Australia

Site Status

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

CHU de Liège (Sart Tilman)

Liège, , Belgium

Site Status

Peking University Third Hospital

Beijing, , China

Site Status

Sun Yet-sen University Cancer Center

Guangzhou, , China

Site Status

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Tianjin Cancer Hospital

Tianjin, , China

Site Status

Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology

Wuhan, , China

Site Status

Zhejiang Cancer Hospital

Zhejiang, , China

Site Status

Henan Cancer Hospital

Zhengzhou, , China

Site Status

Aarhus Universitetshospital Skejby

Aarhus N, , Denmark

Site Status

Rigshospitalet

København Ø, , Denmark

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Hopital Claude Huriez

Lille, , France

Site Status

Chu de Montpellier-St Eloi

Montpellier, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

CHU Pontchaillou

Rennes, , France

Site Status

Universitatsklinikum Frankfurt

Frankfurt, , Germany

Site Status

Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I

Giessen, , Germany

Site Status

Universitaetsklinikum Regensburg

Regensburg, , Germany

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

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

Lublin, , Poland

Site Status

Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, , Poland

Site Status

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, , Poland

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clínic i Provincial

Barcelona, , Spain

Site Status

Hospital Universitario la Paz

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Inselspital Bern, Insel-Gruppe AG

Bern, , Switzerland

Site Status

Universitätsspital Zürich

Zurich, , Switzerland

Site Status

Chang Gung Medical Foundation - Kaohsiung;Oncology

Kaoisung, , Taiwan

Site Status

Chang Gung Medical Foundation - Linkou

Taoyuan District, , Taiwan

Site Status

Taichung Veterans General Hospital

Xitun Dist., , Taiwan

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

St James's Institute of Oncology

Leeds, , United Kingdom

Site Status

UCLH - Clinical Trials Pharmacy B&D Centre

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Countries

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United States Australia Belgium China Denmark France Germany Poland South Korea Spain Switzerland Taiwan United Kingdom

References

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Sam J, Leclercq-Cohen G, Gebhardt S, Surowka M, Herter S, Lechner K, Relf J, Briner S, Varol A, Appelt B, Domocos I, Nicolini V, Bez M, Bommer E, Jenni S, Schoenle A, Le Clech M, Colombetti S, Klein C, Umana P, Lundberg P, Korfi K, Bottos A, Bacac M. Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma. Blood. 2025 Oct 9;146(15):1824-1836. doi: 10.1182/blood.2025028863.

Reference Type DERIVED
PMID: 40749164 (View on PubMed)

Abramson JS, Ku M, Hertzberg M, Huang HQ, Fox CP, Zhang H, Yoon DH, Kim WS, Abdulhaq H, Townsend W, Herbaux C, Zaucha JM, Zhang QY, Chang H, Liu Y, Cheah CY, Ghesquieres H, Simko S, Orellana-Noia V, Ta R, Relf J, Dixon M, Kallemeijn M, Mulvihill E, Huang H, Lundberg L, Gregory GP. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024 Nov 16;404(10466):1940-1954. doi: 10.1016/S0140-6736(24)01774-4.

Reference Type DERIVED
PMID: 39550172 (View on PubMed)

Other Identifiers

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2020-001021-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO41944

Identifier Type: -

Identifier Source: org_study_id

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