A Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

September 25, 2023 updated by: Hoffmann-La Roche

A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

This study is designed to evaluate the safety and efficacy of glofitamab or mosunetuzumab in combination with gemcitabine and oxaliplatin (Glofit-GemOx or Mosun-GemOx) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
23

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Prince of Wales Hospital; Haematology
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health Monash Medical Centre
      • Fitzroy, Victoria, Australia, 3065
        • St Vincent's Hospital Melbourne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0,1, or 2
  • Histologically confirmed B-cell lymphoma, including one of the following diagnoses per the 2016 World Health Organization (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); HGBCL with MYC and BCL2 and/or BCL6 rearrangements; HGBCL, NOS
  • R/R disease, defined as follows: Relapse: disease that has recurred following a response that lasted >/=6 months after completion of last line of therapy; Refractory: disease that progressed during therapy or progressed within 6 months (<6 months) of prior therapy
  • At least one line of prior systemic therapy
  • At least one bi-dimensionally measurable nodal lesion or one bi-dimensionally measurable extranodal lesion, as measured on positron emission tomography-computed tomography (PET/CT) scan
  • Adequate hematologic function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as follows: Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 18 months after the final dose of obinutuzumab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, 3 months after the final dose of mosunetuzumab, 3 months after the final dose of tocilizumab, and 2 months after the final dose of glofitamab. Women must refrain from donating eggs during this same period
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as follows: With a female partner of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 2 months after the final dose of glofitamab, 2 months after the final dose of mosunetuzumab, 2 months after the final dose of tocilizumab (if applicable), 3 months after the final dose of obinutuzumab, and 6 months after the final dose of oxaliplatin or gemcitabine to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

Exclusion Criteria

  • Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
  • 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, gemcitabine, oxaliplatin, or tocilizumab
  • Prior treatment with a bispecific antibody targeting both CD20 and CD3, including glofitamab and mosunetuzumab
  • Grade >1 peripheral neuropathy
  • 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 the 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
  • History of other malignancy that could affect compliance with the protocol or interpretation of results
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
  • 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 first study treatment
  • Suspected or latent tuberculosis
  • Positive test results for chronic hepatitis B virus (HBV) infection
  • Positive test results for hepatitis C virus (HCV) antibody
  • Known HIV-seropositive status
  • Known or suspected chronic active Epstein-Barr virus infection
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • History of progressive multifocal leukoencephalopathy
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
  • Administration of a live, attenuated vaccine within 4 weeks prior to the first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
  • Prior solid organ transplantation
  • Prior allogenic 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 the first dose of study treatment
  • Corticosteroid therapy within 2 weeks prior to first dose of study treatment, with exceptions defined by the study protocol
  • Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
  • Clinically significant history of liver disease, including cirrhosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A: Glofit-GemOx
Participants will receive up to 8 cycles of Glofit-GemOx (glofitamab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles, 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.
Drug: Gemcitabine
Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.
Drug: Oxaliplatin
Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.
Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Names:
  • RO4877533
Drug: Glofitamab
Participants will receive intravenous (IV) glofitamab in combination with gemcitabine and oxaliplatin for up to 8 cycles, followed by up to 4 cycles of glofitamab monotherapy.
Other Names:
  • RO7082859
Drug: Obinutuzumab
Participants will receive a single dose of IV obinutuzumab 7 days prior to the first administration of glofitamab.
Other Names:
  • RO5072759
Experimental: Arm B: Mosun-GemOx
Participants will receive up to 8 cycles of Mosun-GemOx (mosunetuzumab in combination with gemcitabine and oxaliplatin) administered in 21-day cycles.
Drug: Gemcitabine
Participants will receive IV gemcitabine prior to oxaliplatin administration for up to 8 cycles.
Drug: Oxaliplatin
Participants will receive IV oxaliplatin after gemcitabine administration for up to 8 cycles.
Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Names:
  • RO4877533
Drug: Mosunetuzumab
Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles.
Other Names:
  • RO7030816

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Deaths Due to Adverse Events (AEs)
Time Frame: Baseline - 90 days after last dose of study treatment
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
Baseline - 90 days after last dose of study treatment
Number of Treatment Discontinuations Due to AE
Time Frame: Baseline - 90 days after last dose of study treatment
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
Baseline - 90 days after last dose of study treatment
Proportion of Participants With Serious Adverse Events (SAEs)
Time Frame: Baseline - 90 days after last dose of study treatment
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
Baseline - 90 days after last dose of study treatment
Proportion of Participants With Cytokine Release Syndrome (CRS) by Grade of Severity
Time Frame: Baseline - 90 days after last dose of study treatment
Severity of CRS was determined according to the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Criteria, in which Grade 1 as fever (≥38.0°C) with or without other symptoms; Grade 2 as fever with hypotension not requiring vasopressors and/or hypoxia requiring the use of oxygen (low-flow); and Grade 3 as fever with hypotension requiring one vasopressor with or without vasopressin and/or hypoxia requiring the use of oxygen (high-flow).
Baseline - 90 days after last dose of study treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tolerability of Study Treatment as Measured by Dose Interruptions, Dose Reductions, and Treatment Discontinuation Due to AEs
Time Frame: Up to approximately 16 months
Up to approximately 16 months
Complete Response (CR) Based on PET/CT as Determined by the Investigator According to the 2014 Lugano Response Criteria
Time Frame: Up to approximately 16 months
Per the 2014 Lugano Response Criteria for malignant lymphoma a CR = complete metabolic response with a score of 1, 2, or 3 on a 5-point scale (5PS), with higher scores indicating more extensive disease.
Up to approximately 16 months
Objective Response Rate (ORR), Defined as the Proportion of Participants With a Best Overall Response of Partial Response (PR) or CR, as Determined by the Investigator According to the 2014 Lugano Response Criteria
Time Frame: Up to approximately 16 months
Per the 2014 Lugano Response Criteria for malignant lymphoma a CR = complete metabolic response with a score of 1, 2, or 3 on a 5-point scale (5PS), while a PR = partial metabolic response with a score of 4 or 5 on 5PS with higher scores indicating more extensive disease.
Up to approximately 16 months
Maximum Serum Concentration (Cmax) of Glofitamab
Time Frame: Cycle 1 Day 8 and Cycle 2 Day 1
Cycle 1 Day 8 and Cycle 2 Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 4, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 26, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 26, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GO41943

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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