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

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Glofitamab in Combination With Gemcitabine Plus Oxaliplatin Versus Rituximab in Combination With Gemcitabine and Oxaliplatin in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04408638
• Other study ID #: GO41944
• Secondary ID: 2020-001021-31
• Status: Recruiting
• Phase: Phase 3
• Start date: February 23, 2021
• Est. completion date: April 15, 2025

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: GO41944 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: April 15, 2025
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Obinutuzumab
Participants will receive a single dose of intravenous (IV) obinutuzumab pre-treatment 7 days prior to the first dose of glofitamab.
• Glofitamab
Participants will receive IV glofitamab for up to 12 cycles.
• Rituxumab
Participants will receive IV rituxumab on Day 1 of each cycle for up to 8 cycles.
• Tocilizumab
Participants will receive IV tocilizumab as needed for treatment of cytokine-release syndrome (CRS).
• Gemcitabine
Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.
• Oxaliplatin
Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital; Haematology Clinical Trials	Adelaide	South Australia
Australia	Monash Health Monash Medical Centre	Clayton	Victoria
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Prince of Wales Hospital; Haematology	Randwick	New South Wales
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHU Sart-Tilman	Liège
China	Beijing Cancer Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	West China Hospital, Sichuan University	Chengdu
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Jiangsu Province Hospital	Nanjing
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Tianjin Cancer Hospital	Tianjin
China	Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology	Wuhan City
China	Zhejiang Cancer Hospital	Zhejiang
China	Henan Cancer Hospital	Zhengzhou
Denmark	Aarhus Universitetshospital Skejby; Blodsygdomme	Aarhus N
Denmark	Rigshospitalet; Hæmatologisk Klinik	København Ø
France	Institut Bergonie; Hematologie Oncologie	Bordeaux
France	Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny	Creteil
France	Hopital Claude Huriez; Hematologie	Lille
France	CHU DE MONTPELLIER-ST ELOI; Département d'Hématologie Clinique	Montpellier
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU Pontchaillou; Service Hématologie	Rennes
Germany	Städtisches Klinikum Dessau	Dessau-Roßlau
Germany	Universitatsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I	Giessen
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Regensburg	Regensburg
Germany	Katharinenhospital Stuttgart; Klinik für Hämatologie, Onkologie und Palliativmedizin	Stuttgart
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli	Lublin
Poland	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej	Opole
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku	Pozna?
Poland	Instytut Hematologii i Transfuzjologii; Klinika Hematologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wroc?aw
Puerto Rico	PanOncology Trials; Hospital Oncológico, Puerto Rico Medical Center	San Juan
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona
Spain	Hospital Universitario la Paz; Servicio de Hematologia	Madrid
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Hematologia	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Switzerland	Inselspital Bern, Insel-Gruppe AG	Bern
Switzerland	Universitätsspital Zürich	Zürich
Taiwan	Chang Gung Medical Foundation - Kaohsiung; Oncology; Division of Hematology-Oncology	Kaoisung
Taiwan	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan
Taiwan	Taichung Veterans General Hospital	Xitun Dist.
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James's Institute of Oncology; Dept of Haematology	Leeds
United Kingdom	UCLH - Clinical Trials Pharmacy B&D Centre	London
United Kingdom	Christie Hospital; Department of Haematology and Transplant	Manchester
United Kingdom	Nottingham City Hospital; Dept of Haematology	Nottingham
United Kingdom	Southampton General Hospital	Southampton
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Community Cancer Institute (CCI)	Fresno	California
United States	Banner Health MD Anderson AZ	Gilbert	Arizona
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist - MD Anderson Cancer Center	Jacksonville	Florida
United States	Baptist Medical Center - Jacksonville	Jacksonville	Florida
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  China,  Denmark,  France,  Germany,  Korea, Republic of,  Poland,  Puerto Rico,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS), defined as the time from randomization to date of death from any cause		Up to 5 years
Secondary	Progression-free survival (PFS), defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the Independent Review Committee (IRC)		Up to 5 years
Secondary	PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator		Up to 5 years
Secondary	Complete response (CR) rate, defined as the proportion of patients whose best overall response is a CR on positron emission tomography/computed tomography (PET/CT) during the study, as determined by the IRC		Up to 5 years
Secondary	CR rate, defined as the proportion of patients whose best overall response is a CR on positron emission tomography/computed tomography (PET/CT) during the study, as determined by the investigator		Up to 5 years
Secondary	Objective response rate (ORR), defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by the IRC		Up to 5 years
Secondary	ORR, defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by the investigator		Up to 5 years
Secondary	Duration of objective response (DOR), defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression, or death from any cause, whichever occurs first		Up to 5 years
Secondary	Duration of CR, defined as the time from the first occurrence of a documented CR to disease progression, or death from any cause, whichever occurs first		Up to 5 years
Secondary	Time to deterioration in physical functioning and fatigue, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)		Up to 5 years
Secondary	Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LymS)		Up to 5 years
Secondary	Percentage of Participants with Adverse Events		Up to 5 years
Secondary	Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events		Up to 5 years