A Study to Evaluate the Efficacy and Safety of Glofitamab in Combination with Gemcitabine Plus Oxaliplatin Versus Rituximab in Combination with Gemcitabine Plus Oxaliplatin in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Conditions
- Relapsed or refractory diffuse large B-cell lymphomaMedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001021-31-BE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 270
•Age >= 18 years
•Life expectancy >= 12 weeks
•Histologically confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS)
•Relapsed or refractory disease
•At least one line of prior systemic therapy
•Patients who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant
•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 nodal lesion, or one bi-dimensionally measurable extranodal lesion, as measured on CT scan
•Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
•Adequate hematologic function; adequate renal function
•For women of childbearing potential: agreement to remain abstinent or use contraceptive measures with a failure rate of <1% per year, and agreement to refrain from donating eggs, during the treatment period and for at least 18 months after the final dose of obinutuzumab, 12 months after the final dose of rituximab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, 3 months after the final dose of tocilizumab, and 2 months after the final dose of glofitamab.
•For men: with a female partner of childbearing potential or a pregnant female partner, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year, and men must agree to refrain from donating sperm, during the treatment period and for at least 6 months after the final dose of oxaliplatin or gemcitabine, 3 months after final dose of rituximab or obinutuzumab, and 2 months after the final dose of glofitamab or tocilizumab to avoid exposing the embryo.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
•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 NOS, as defined by to 2016 WHO guidelines
•Primary mediastinal B-cell lymphoma
•History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies 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
•Prior treatment with R-GemOx or GemOx
•Peripheral neuropathy assessed to be Grade >1 according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (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
•History of other malignancy that could affect compliance with the protocol or interpretation of results
•Cardiovascular disease or significant pulmonary disease
•Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment
•Positive test results for hepatitis B virus infection and hepatitis C virus antibody
•Known history of human immunodeficiency virus (HIV) seropositive status, known or suspected chronic active Epstein-Barr viral infection, hemophagocytic lymphohistiocytosis, history of progressive multifocal leukoencephalopathy
•Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better
•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, within 4 weeks prior to first dose of study treatment
•Corticosteroid therapy within 2 weeks prior to first dose of study treatment, except for acute low-dose steroids
•Recent major surgery other than for diagnosis
•Clinically significant history of cirrhotic liver disease
•Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
•Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 18 months after the final dose of study treatment
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To evaluate the efficacy of glofitamab (Glofit)- gemcitabine plus oxaliplatin (GemOx) compared with rituximab in combination with gemcitabine and oxaliplatin (R-GemOx) on the basis of overall survival;Secondary Objective: •To evaluate the efficacy of Glofit-GemOx compared with R-GemOx on the basis of progression-free survival, complete response rate, objective response rate, duration of objective response, duration of complete response, time to deterioration in physical functioning and fatigue<br>•To evaluate the safety and tolerability of Glofit-GemOx compared with R-GemOx<br>•To evaluate the pharmacokinetics of Glofit when administered as a component of Glofit-GemOx<br>•To evaluate the pharmacokinetics of obinutuzumab<br>•To evaluate the immune response to Glofit-GemOx;Primary end point(s): 1.Overall Survival;Timepoint(s) of evaluation of this end point: 1. Up to 3.5 years
- Secondary Outcome Measures
Name Time Method