This is an investigator-initiated, open-label, single-arm, multicenter, Phase II clinical study. The study is designed to evaluate the safety and potential effectiveness of glofitamab in adults with their disease, diffuse large B-cell lymphoma (DLBCL has either not responded to initial treatment or has returned after an initial response and who are eligible and medically fit for autologous stem cell transplantation (ASCT). Autologous stem cell transplantation is a commonly used treatment in this situation and involves high-dose chemotherapy followed by infusion of your own stem cells, which are collected from your blood several weeks before the transplant.
The purpose of this study is to assess glofitamab, which is not part of standard treatment. Glofitamab is a type of antibody designed to attach to both lymphoma cells and certain immune cells called T cells. By bringing these cells together, glofitamab may help activate the immune system so that T cells can better recognize and destroy lymphoma cells. In this study, glofitamab may be used as a "bridge" to transplantation and/or as consolidation treatment after the transplant, depending on how the disease responds to chemotherapy given before the transplant.
In recent years, newer immune-based treatments such as CAR-T cell therapy have shown benefit for patients whose lymphoma does not respond to or returns after chemotherapy. CAR-T therapy involves collecting immune cells, modifying them in a laboratory, and then reinfusing them into the patient. However, access to CAR-T therapy is limited in some regions, including Lebanon, and autologous stem cell transplantation remains an important treatment option
Provision of signed and dated informed consent form (ICF) ) by the patient/impartial witness/legal representative before any trial related procedures.
Male or female aged between 18 and 65 years.
Ability and willingness to comply with the study protocol.
Histologically confirmed diagnosis of primary refractory or relapsed DLBCL (all subtypes including primary mediastinal B cell lymphoma, high grade B cell lymphoma, large B cell lymphoma etc) or transformed low grade B cell lymphoma planned for salvage Rituximab-chemotherapy regimens followed by ASCT.
Patients receiving any investigational drug, biological, immunological therapy within the previous 21 days before enrollment.
Presence of any severe or uncontrolled systemic disease or condition, including serious cardiac, pulmonary or renal conditions; any type of bacterial, viral, fungal or other infection that would pose a significant risk to the patient in the opinion of the investigator; or active Hepatitis B or positive HCV antibodies.
Any unresolved toxicities from prior therapy, greater than CTCAE-version 5 grade 2 at the time of starting study treatment, with exception of alopecia.
Congestive heart failure (CHF) currently requiring therapy and patients with New York Heart Association Class III/IV CHF
Single group
Glofitamab
DrugGlofitamab is started with initially a step-up dosing of 2.5 mg on C1D1 then 10 mg on C1D8 to be followed by 30 mg every 3 weeks for a total of 3 cycles. Disease evaluation is repeated after completion of 3 cycles of Glofitamab, and patients achieving PR or better then undergo ASCT followed by 3 cycles post consolidation glofitamab (30 mg every 3 weeks).
To evaluate the efficacy of glofitamab when used as a bridge to and/or consolidation post-transplant for patients with relapsed/refractory B-cell lymphomas (DLBCL or transformed low grade B cell lymphoma) fit and eligible for ASCT
Progression free survival (PFS) at 1 year post relapse-defined as the time from infusion of first salvage chemotherapy to the first occurrence of disease progression or death from any cause, whichever occurs first as determined by the investigator
To evaluate the 3 years overall survival
Overall survival (OS) at 3 year post relapse defined as the time from first dose of salvage chemotherapy to date of death from any cause
To evaluate the safety and tolerability of glofitamab in this setting
Incidence and severity of adverse events (AEs), with severity determined according to the national Cancer Institute Common Toxicity Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
To evaluate the effect of glofitamab when used as a bridge to and/or consolidation post ASCT on health-related quality of life (HRQoL)
Changes in QLQ-NHL-HG29 questionnaire results taken before first dose of glofitamab and that taken at end of treatment with glofitamab. he EORTC QLQ-NHL-HG29 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Hodgkin Lymphoma-High-Grade 29) is a disease-specific quality-of-life instrument. Scores are transformed to a 0-100 scale. For functional domains, higher scores indicate better outcomes, whereas for symptom domains, higher scores indicate worse outcomes.
To evaluate the effect of treatment with glofitamab on acute phase reactants such as fibrinogen and its clinical significance
Changes in fibrinogen level from baseline (before starting first dose of glofitamab compared to post each dose of glofitamab and post last dose of glofitamab) will be correlated with PFS and CRS.
Click on the lead sponsor to view all of their trials.
American University of Beirut Medical Center
Lead sponsor
Roche Pharma AG
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
