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Odronextamab for the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma Before and After Chimeric Antigen Receptor T-cell Therapy

ConditionsRecurrent Diffuse Large B-Cell LymphomaRecurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, Davis

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged ≥ 18 at the time of consent

Patients must have histologically or cytologically confirmed relapsed/ refractory (R/R) diffuse large B-cell lymphoma (DLBCL); transformed follicular lymphoma patients are eligible

Patients must have failed at least 2 prior therapies

Life expectancy ≥ 3 months

Disqualifiers

Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she/they were to participate in the study or confounds the ability to interpret data from the study as determined by the study principal investigator (PI) or enrolling physician

Known involvement by primary central nervous system (CNS) lymphoma or known uncontrolled involvement by non-primary CNS non-Hodgkin lymphoma (NHL) at the time of study entry

Epilepsy, seizure, paresis, aphasia, apoplexy, severe brain injury, cerebellar disease, organic brain syndrome, psychosis, cerebrovascular stroke or

Evidence for presence of inflammatory lesions and/or vasculitis on cerebral magnetic resonance imaging (MRI)

Trial design

Design model

Single group

Treatments tested in this trial

  • Chimeric Antigen Receptor T-Cell Therapy

    Biological/Vaccine

    Receive CAR T-cell therapy

  • Odronextamab

    Biological/Vaccine

    Given IV

Treatment groups

34 Participants
are divided into 1 treatment group
Group A: Treatment (odronextamab, CAR T-cell therapy)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Complete 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

Secondary outcomes

1

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
2

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
3

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
4

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)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, Davis

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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