This phase II trial tests the effectiveness of odronextamab given before chimeric antigen receptor T (CAR-T) cell therapy (bridging therapy) in patients with large B-cell lymphomas that have come back after a period of improvement (relapsed) or that have not responded to previous treatment (refractory). Odronextamab is a bispecific antibody that can bind to two different antigens at the same time. Odronextamab binds to CD3, a T-cell surface antigen, and CD20 (a tumor-associated antigen that is expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell cancers) and may interfere with the ability of cancer cells to grow and spread. Bridging therapy has been used to maintain disease control and to increase the chance of successful receipt of CAR-T cell therapy. However, bridging therapy is typically given after leukapheresis, which does not help prevent disease progression between the decision for CAR-T cell therapy and leukapheresis. Giving odronextamab as bridging therapy before leukapheresis may delay disease progression to allow leukapheresis and increase the likelihood of successful CAR-T cell therapy in patients with relapsed or refractory large B-cell lymphomas.
OUTLINE: Patients receive odronextamab intravenously (IV) on days 1, 2, 8, 9, 15 and 16 of cycle 1 (dose step-up), and on days 1, 8 and 15 of cycles 2-4 and then once every other week of remaining cycles. Cycles repeat every 21 days for the first 4 cycles, then every other week for up to a total of 12 months (including the first 2 cycles). After 2 cycles, patients undergo leukapheresis followed by lymphodepletion and CAR-T infusion per standard of care. If there is a significant delay of leukapheresis, patients may receive up to 12 additional weeks of treatment. Patients who achieve CR after cycle 2 may opt out of leukapheresis and CAR-T cell infusion and may continue to receive odronextamab in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/computed tomography (CT), collection of blood and oral or rectal swab samples and tissue biopsy throughout the study. Additionally, patients may undergo lumbar puncture and bone marrow aspiration and/or biopsy on study. After completion of study treatment, patients are followed till 90 days or the initiation of the next lymphoma directed therapy for toxicity check, and total duration of follow-up is up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Given IV
Undergo collection of blood and oral or rectal swab samples
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CAR-T cell therapy
Undergo PET/CT
Undergo leukapheresis
Undergo lumbar puncture
Undergo PET/CT
Ancillary studies
Undergo tissue biopsy
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGFailure to undergo leukapheresis
Will include failures due to disease progression or adverse events (AEs) due to odronextamab (Odron), or requirement of other lymphoma-directed therapy for bridging before leukapheresis due to lack of response. Will report the total number and percentage with 95% confidence interval (CI).
Time frame: Up to 5 years
Receipt of chimeric antigen receptor T-cell therapy (CAR-T)
Will estimate the total number and percentage with 95% CI of patients who receive CAR-T cell infusion. Patients who achieve complete response (CR) after 2 cycles of Odron and opt out of leukapheresis will be excluded from the estimation of the percentage. Will also report the reasons why patients do not eventually receive CAR-T.
Time frame: Up to 5 years
Overall response rate (ORR) following bridging prior to CAR-T infusion
ORR includes CR, partial response, stable disease. Will report the total number and percentage with 95% CI of patients who achieve response on positron emission tomography/computed tomography (PET/CT) scans before CAR-T cell infusion. Patients who receive CAR-T cell infusion will be included in the estimation of this percentage.
Time frame: Up to 5 years
Progression free survival (PFS) following CAR-T infusion
Will estimate the median with interquartile range of the progression free duration. Will also report the percentage with 95% CI.
Time frame: Up to 2 years
CR rate
Will report the total number and percentage with 95% CI of patients who achieve CR on the PET/CT scans following CAR-T cell infusion.
Time frame: At 1 month after CAR-T
PFS in patients who achieve CR after 2 cycles of Odron, choose to opt out of CART, and receive up to a total of 12 months of Odron
Will report the median duration of PFS with 95% CI in this group of patients.
Time frame: Up to 5 years
Incidence of AEs
All AEs will be graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Cytokine release syndrome and immune effector cell associated neurotoxicity syndrome will be graded by the American Society for Transplantation and Cellular Therapy Consensus Grading systems. Will report the rate and grade of each AE, including unsuccessful CAR-T production.
Time frame: Up to 90 days after the last dose of Odron or the initiation of the next lymphoma directed therapy, whichever occurs first
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