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.
PRIMARY OBJECTIVE: I. To determine the proportion of relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients with an objective response (OR) to glofitamab after prior treatment with chimeric antigen receptor (CAR)-T. SECONDARY OBJECTIVES: I. To describe the proportion of patients with a complete response (CR). II. To describe the progression-free survival (PFS) and overall survival (OS) at 24 months. III. To describe the incidence of grade 3-4 cytokine release syndrome (CRS). IV. To describe the incidence of grade 3-4 neurologic toxicity. V. To describe the relationship between glofitamab clearance at baseline, changes in clearance over time, treatment response, and duration of response. EXPLORATORY OBJECTIVES: I. To evaluate the relationship between circulating tumor deoxyribonucleic acid (DNA) (ctDNA) detection in plasma, treatment response, and duration of response. II. To evaluate the relationship between CAR T-cell levels in plasma, immunophenotype, treatment response, and duration of response. III. To evaluate the relationship between fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) interlesional treatment response heterogeneity and survival outcomes. IV. To evaluate the relationship between organ-specific changes in standardized uptake value (SUV) metrics and immune-related adverse events (AEs). OUTLINE: Patients receive obinutuzumab intravenously (IV) on day 1 or on days 1 and 2 of cycle 1 and glofitamab IV over 8 hours on days 8 and 15 of cycle 1 then over 2-8 hours on day 1 of cycles 2-12. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET/CT throughout the study. After completion of study treatment, patients are followed every 3 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Undergo blood sample collection
Undergo PET/CT
Given IV
Given IV
Undergo PET/CT
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Baltimore, Maryland, United States
RECRUITINGObjective response rate
A Simon 2-stage optimal design will be used with a favorable response of 55% and unfavorable response of 25%.
Time frame: Up to 2 years
Complete response rate
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals.
Time frame: Up to 2 years
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.
Time frame: Up to 24 months
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.
Time frame: Up to 24 months
Incidence of grade 3-4 cytokine release syndrome
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals. Incidence will be described.
Time frame: Up to 2 years
Incidence of grade 3-4 neurologic toxicity
Proportions will be estimated with Agresti-Coull 95% binomial confidence intervals. Incidence will be described.
Time frame: Up to 2 years
Changes in glofitamab clearance
Pharmacokinetics (PK) of glofitamab will also be determined to assess exposure-response and clearance-response relationships. When appropriate, Bayesian logistic regression analysis will be performed to assess exposure-response and clearance-response relationships. Basic non-compartmental analyses will be performed with the concentration versus time data to summarize several pharmacokinetic parameters including observed maximum concentration and area under the observed concentration versus time curves. Descriptive statistics will be used to summarize these results. Nonlinear mixed-effects modeling will also be performed to develop a population PK model of glofitamab to describe PK properties, including absorption, distribution, and overall elimination.
Time frame: At baseline and up to 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.