This phase II trial tests the safety and side effects of glofitamab and obinutuzumab and how well they work in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory) after receiving CD19-directed chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a form of immunotherapy where the immune system cell, T-cell, is changed to attack cancer cells. Glofitamab is a bispecific antibody that can bind to two different antigens at the same time. Glofitamab binds to CD3, a protein found on T cells (a type of white blood cell), and CD20 a protein found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving glofitamab and obinutuzumab may be safe, tolerable, and/or effective in treating patients with relapsed or refractory mantle cell lymphoma after receiving CD19-directed CAR T-cell therapy.
Patients must have histologically or cytologically confirmed diagnosis of mantle cell lymphoma that is relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen)
Patients must have been previously treated with an anti-CD19 CAR T-cell therapy and have failed or been intolerant to Bruton's tyrosine kinase (BTK) inhibition. Both commercial and investigational CAR-T products which target CD19 will be allowed, including dual-targeting products
Patients must have at least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan
Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of glofitamab and obinutuzumab in patients < 18 years of age, children are excluded from this study
Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to glofitamab and obinutuzumab
Pregnant women are excluded from this study because glofitamab and obinutuzumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with glofitamab and obinutuzumab, breastfeeding should be discontinued if the mother is treated with glofitamab and obinutuzumab
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo PET/CT
Glofitamab
Biological/VaccineGiven IV
Obinutuzumab
Biological/VaccineGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Objective response rate
A Simon 2-stage optimal design will be used with a favorable response of 55% and unfavorable response of 25%.
Complete response rate
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals.
Progression-free survival (PFS)
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals. Will be estimated using the Kaplan Meier method. Estimates of PFS will be reported with a 95% confidence interval.
Overall survival (OS)
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals. Will be estimated using the Kaplan Meier method. Estimates of OS will be reported with a 95% confidence interval.
Incidence of grade 3-4 cytokine release syndrome
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals. Incidence will be described.
Relationship in circulating tumor deoxyribonucleic acid (ctDNA) in plasma, treatment response, and duration of response
Descriptive statistics will be used to summarize the ctDNA results.
Relationship between chimeric antigen receptor (CAR) T-cell levels in plasma, immunophenotype, treatment response, and duration of response
Descriptive statistics will be used to summarize the CAR-T and T-cell immunophenotype results.
Glofitamab PK
Relationship between fluorodeoxyglucose positron emission tomography/ computed tomography interlesional treatment response heterogeneity and survival outcomes
Responses will be assessed using 2014 revised response criteria as outlined by Cheson et al., 2014.
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