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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04313608
Recruitment Status : Recruiting
First Posted : March 18, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
B-cell Lymphoma Drug: Glofitamab Drug: Gemcitabine Drug: Oxaliplatin Drug: Mosunetuzumab Drug: Obinutuzumab Drug: Tocilizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 4, 2020
Estimated Primary Completion Date : March 6, 2021
Estimated Study Completion Date : March 6, 2021


Arm Intervention/treatment
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: 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 Name: RO7082859

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: Obinutuzumab
Participants will receive a single dose of IV obinutuzumab 7 days prior to the first administration of glofitamab.
Other Name: RO5072759

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Name: RO4877533

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: Mosunetuzumab
Participants will receive IV mosunetuzumab in combination with gemcitabine and oxaliplatin for up to 8 cycles.
Other Name: RO7030816

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to treat cytokine release syndrome (CRS).
Other Name: RO4877533




Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 17 months ]

Secondary Outcome Measures :
  1. Tolerability of Study Treatment as Measured by Dose Interruptions, Dose Reductions, Dose Intensity, and Treatment Discontinuation due to AEs [ Time Frame: Up to 17 months ]
  2. Complete Response (CR) Based on PET/CT as Determined by the Investigator According to the 2014 Lugano Response Criteria [ Time Frame: Up to 17 months ]
  3. 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 17 months ]
  4. Minimum Serum Concentration (Cmin) of the CD20-CD3 Bispecific Antibody [ Time Frame: At pre-defined intervals from baseline up to 17 months ]
  5. Maximum Serum Concentration (Cmax) of the CD20-CD3 Bispecific Antibody [ Time Frame: At pre-defined intervals from baseline up to 17 months ]
  6. Area Under the Concentration-Time Curve (AUC) of the CD20-CD3 Bispecific Antibody [ Time Frame: At pre-defined intervals from baseline up to 17 months ]
  7. Proportion of Participants with Anti-Drug Antibodies (ADAs) to Glofitamab [ Time Frame: Baseline up to 17 months ]
  8. Proportion of Participants with ADAs to Mosunetuzumab [ Time Frame: Baseline up to 17 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04313608


Contacts
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Contact: Reference Study ID Number: GO41943 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 global-roche-genentech-trials@gene.com

Locations
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Australia, New South Wales
Prince of Wales Hospital; Haematology Recruiting
Randwick, New South Wales, Australia, 2031
Australia, Victoria
Monash Health Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
St Vincent's Hospital Melbourne Recruiting
Fitzroy, Victoria, Australia, 3065
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04313608    
Other Study ID Numbers: GO41943
First Posted: March 18, 2020    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Oxaliplatin
Obinutuzumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological