This phase II trial tests how well odronextamab works before and after standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapy in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR-T cell therapy is the SOC treatment most patients receive when other treatments have failed. CAR-T cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Odronextamab is a monoclonal antibody that is called bispecific, as it individually targets 2 cell proteins, CD20 and CD3. Proteins are part of each cell in the body, which work together like little machines for the cell to function. CD20 is a protein that is found on the surface of both normal B-cells and B-cells that make up certain cancers, like DLBCL. CD3 is a protein that is found on the surface of T cells. T-cells and normal B-cells are types of white blood cells in the body and are a part of the immune system that fights infections. Odronextamab is designed to help T-cells find and kill the B-cells including the cancer cells in DLBCL. Giving odronextamab before and after CAR T-cell therapy may improve response in patients with relapsed or refractory DLBCL.
PRIMARY OBJECTIVE: I. To assess anti-tumor activity of odronextamab + CAR T-cell therapy in in patients with relapsed or refractory (R/R) DLBCL. SECONDARY OBJECTIVES: I. To evaluate the toxicities of odronextamab + CAR T-cell therapy in patients with R/R DLBCL. II. To further assess anti-tumor activity of odronextamab + CAR T-cell therapy in patients with R/R DLBCL. OUTLINE: Patients receive odronextamab intravenously (IV) over 1-4 hours on days 1, 2, 8, 9, 15, and 16 of cycle 1, on days 1, 8, and 15 of cycles 2-4 then on days 1 and 15 of subsequent cycles until achievement of durable complete response (CR). Cycles repeat every 21 days in the absence of durable CR, disease progression, or unacceptable toxicity. Patients with durable CR for ≥ 9 months may then receive odronextamab IV over 1-4 hours on day 1 of each subsequent cycle. These cycles repeat every 28 days for up to a total of 2 years in the absence of disease progression or unacceptable toxicity. Patients receive SOC CAR T-cell therapy if disease assessment shows less than a CR after cycle 4, or after cycle 5 if disease assessment shows progressive disease (PD) any time after cycle 5. Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and blood sample collection, positron emission tomography (PET)/computed tomography (CT) or CT throughout the study. Patients may also undergo CT of the brain at screening. After completion of study treatment, patients are followed up at 30 days then every 4 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Receive CAR T-cell therapy
Given IV
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGComplete response rate (CRR)
Will be assessed by Lugano 2014. Will calculate the uniformly minimum variance unbiased estimator, p-value, and confidence intervals for CRR. The calculation will be performed using R clinfun package.
Time frame: From first dose through completion of 5 cycles (cycle length = 21 days for cycles 1-4 and 14 days for cycle 5) of odronextamab and chimeric antigen receptor (CAR) T cell infusion
Number of participants experiencing treatment-related adverse events (AEs)
Will be classified by severity, and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The proportion of subjects experiencing AEs, serious AEs, and treatment delays will be summarized. All AEs will be listed, documenting the course, outcome, severity, and relationship to the study treatment. Incidence rates of AEs and the proportion of subjects prematurely withdrawn from the study due to AEs will be reported.
Time frame: From first dose through 30 days post last odronextamab dose
Number of participants with progression-free survival
Will be summarized using Kaplan-Meier methodology using 25th, 50th (median), and 75th percentiles with associated 2-sided 95% confidence intervals (CIs), as well as number and percentage of censored observations.
Time frame: From the date of first odronextamab dose until the first occurrence of disease progression, or death from any cause, whichever occurs earlier, assessed up to 2 years
Objective response rate
Will be assessed by Lugano 2014. Data will be presented using descriptive statistics. Tabulations will be produced for appropriate disposition, demographic, baseline, efficacy, and safety parameters. For categorical variables, summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented, as well as 2-sided 95% CIs, unless stated otherwise. For continuous variables, the number of patients, mean, median, standard deviation, minimum, and maximum values will be presented.
Time frame: From first dose to up to 2 years post last odronextamab dose
Number of minimal residual disease (MRD) negative targets detected
Will use circulating tumor-derived deoxyribonucleic acid testing. Data will be presented using descriptive statistics. Tabulations will be produced for appropriate disposition, demographic, baseline, efficacy, and safety parameters. For categorical variables, summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented, as well as 2-sided 95% CIs, unless stated otherwise. For continuous variables, the number of patients, mean, median, standard deviation, minimum, and maximum values will be presented.
Time frame: After cycle 4 (pre-CAR T-cell therapy) and 2 cycles post CAR T cell infusion (cycle length = 21 days for cycles 1-4 and 14 days for subsequent cycles)
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