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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

NCT04408638

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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
  • 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 IDs

  • ORG STUDY ID: GO41944
  • SECONDARY ID: 2020-001021-31
  • NCT ID: NCT04408638

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
ObinutuzumabGlofit-GemOx
GlofitamabGlofit-GemOx
RituxumabR-GemOx
TocilizumabGlofit-GemOx
GemcitabineGlofit-GemOx
OxaliplatinGlofit-GemOx

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Glofit-GemOxExperimentalParticipants 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.
  • Obinutuzumab
  • Glofitamab
  • Tocilizumab
  • Gemcitabine
  • Oxaliplatin
R-GemOxExperimentalParticipants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.
  • Rituxumab
  • Gemcitabine
  • Oxaliplatin

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS), defined as the time from randomization to date of death from any cause
Time Frame:Up to 3.5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events
Time Frame:Up to 3.5 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

May 26, 2020