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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

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: NCT04408638
Recruitment Status : Not yet recruiting
First Posted : May 29, 2020
Last Update Posted : July 23, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: Obinutuzumab Drug: Glofitamab Drug: Rituxumab Drug: Tocilizumab Drug: Gemcitabine Drug: Oxaliplatin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : March 1, 2022
Estimated Study Completion Date : March 1, 2022


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

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

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

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.

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




Primary Outcome Measures :
  1. Overall survival (OS), defined as the time from randomization to date of death from any cause [ Time Frame: Up to 3.5 years ]

Secondary Outcome Measures :
  1. 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) [ Time Frame: Up to 3.5 years ]
  2. 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 [ Time Frame: Up to 3.5 years ]
  3. 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 [ Time Frame: Up to 3.5 years ]
  4. 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 [ Time Frame: Up to 3.5 years ]
  5. 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 [ Time Frame: Up to 3.5 years ]
  6. 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 [ Time Frame: Up to 3.5 years ]
  7. 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 [ Time Frame: Up to 3.5 years ]
  8. 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 [ Time Frame: Up to 3.5 years ]
  9. 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) [ Time Frame: Up to 3.5 years ]
  10. Time to deterioration in lymphoma symptoms, as measured by the Functional Assessment of Cancer Therapy−Lymphoma subscale (FACT-Lym LymS) [ Time Frame: Up to 3.5 years ]
  11. Percentage of Participants with Adverse Events [ Time Frame: Up to 3.5 years ]
  12. Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, and study treatment discontinuation because of adverse events [ Time Frame: Up to 3.5 years ]


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

  • 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
  • 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
  • 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

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): NCT04408638


Contacts
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Contact: Reference Study ID Number: GO41944 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 global-roche-genentech-trials@gene.com

Locations
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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: NCT04408638    
Other Study ID Numbers: GO41944
2020-001021-31 ( EudraCT Number )
First Posted: May 29, 2020    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 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/members/ourmembers/). 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