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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04408638




Registration number
NCT04408638
Ethics application status
Date submitted
26/05/2020
Date registered
29/05/2020

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-001021-31
Secondary ID [2] 0 0
GO41944
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Glofitamab
Treatment: Drugs - Rituxumab
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Oxaliplatin

Experimental: 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.

Experimental: 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.


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

Treatment: Drugs: Glofitamab
Participants will receive IV glofitamab for up to 12 cycles.

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

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

Treatment: Drugs: Gemcitabine
Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.

Treatment: Drugs: Oxaliplatin
Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS), defined as the time from randomization to date of death from any cause
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
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)
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy-Lymphoma subscale (FACT-Lym LymS)
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Percentage of Participants with Adverse Events
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events
Timepoint [12] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/04/2025
Actual
Sample size
Target
270
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Prince of Wales Hospital; Haematology - Randwick
Recruitment hospital [2] 0 0
Royal Adelaide Hospital; Haematology Clinical Trials - Adelaide
Recruitment hospital [3] 0 0
Monash Health Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [6] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Mississippi
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Belgium
State/province [11] 0 0
Liège
Country [12] 0 0
China
State/province [12] 0 0
Beijing
Country [13] 0 0
China
State/province [13] 0 0
Guangzhou City
Country [14] 0 0
China
State/province [14] 0 0
Harbin
Country [15] 0 0
China
State/province [15] 0 0
Shanghai City
Country [16] 0 0
China
State/province [16] 0 0
Tianjin
Country [17] 0 0
China
State/province [17] 0 0
Wuhan City
Country [18] 0 0
China
State/province [18] 0 0
Zhejiang
Country [19] 0 0
China
State/province [19] 0 0
Zhengzhou
Country [20] 0 0
Denmark
State/province [20] 0 0
Aarhus N
Country [21] 0 0
Denmark
State/province [21] 0 0
København Ø
Country [22] 0 0
France
State/province [22] 0 0
Bordeaux
Country [23] 0 0
France
State/province [23] 0 0
Creteil
Country [24] 0 0
France
State/province [24] 0 0
Lille
Country [25] 0 0
France
State/province [25] 0 0
Montpellier
Country [26] 0 0
France
State/province [26] 0 0
Pierre Benite
Country [27] 0 0
France
State/province [27] 0 0
Rennes
Country [28] 0 0
Germany
State/province [28] 0 0
Frankfurt
Country [29] 0 0
Germany
State/province [29] 0 0
Giessen
Country [30] 0 0
Germany
State/province [30] 0 0
Regensburg
Country [31] 0 0
Germany
State/province [31] 0 0
Stuttgart
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Busan
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Goyang-si
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seongnam-si
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Poland
State/province [36] 0 0
Gdansk
Country [37] 0 0
Poland
State/province [37] 0 0
Lublin
Country [38] 0 0
Poland
State/province [38] 0 0
Olsztyn
Country [39] 0 0
Poland
State/province [39] 0 0
Warszawa
Country [40] 0 0
Poland
State/province [40] 0 0
Wroc?aw
Country [41] 0 0
Puerto Rico
State/province [41] 0 0
San Juan
Country [42] 0 0
Spain
State/province [42] 0 0
Cantabria
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Sevilla
Country [46] 0 0
Spain
State/province [46] 0 0
Valencia
Country [47] 0 0
Switzerland
State/province [47] 0 0
Bern
Country [48] 0 0
Switzerland
State/province [48] 0 0
Zürich
Country [49] 0 0
Taiwan
State/province [49] 0 0
Kaoisung
Country [50] 0 0
Taiwan
State/province [50] 0 0
Taoyuan
Country [51] 0 0
Taiwan
State/province [51] 0 0
Xitun Dist.
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Glasgow
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Leeds
Country [54] 0 0
United Kingdom
State/province [54] 0 0
London
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Manchester
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GO41944 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04408638