Odronextamab for Relapsed/Refractory Large B-Cell Lymphomas Before Definitive Lymphoma-Directed Therapies
Summary
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.
Detailed description
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.
Arms & interventions
- BiologicalOdronextamab
Given IV
- ProcedureBiospecimen Collection
Undergo collection of blood and oral or rectal swab samples
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- BiologicalChimeric Antigen Receptor T-Cell Therapy
Undergo CAR-T cell therapy
- ProcedureComputed Tomography
Undergo PET/CT
- ProcedureLeukapheresis
Undergo leukapheresis
- ProcedureLumbar Puncture
Undergo lumbar puncture
- ProcedurePositron Emission Tomography
Undergo PET/CT
- OtherQuestionnaire Administration
Ancillary studies
- ProcedureBiopsy Procedure
Undergo tissue biopsy
Outcome measures
Primary
Failure 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
Secondary
Receipt of chimeric antigen receptor T-cell therapy (CAR-T)
Time frame: Up to 5 years
Overall response rate (ORR) following bridging prior to CAR-T infusion
Time frame: Up to 5 years
Progression free survival (PFS) following CAR-T infusion
Time frame: Up to 2 years
CR rate
Time frame: At 1 month after CAR-T
PFS in patients who achieve CR after 2 cycles of Odron, choose to opt out of CAR-T, and receive up to a total of 12 months of Odron
Time frame: Up to 5 years
Incidence of AEs
Time frame: Up to 90 days after the last dose of Odron or the initiation of the next lymphoma directed therapy, whichever occurs first
Eligibility criteria
Study locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109