Recruiting

Phase 2

OdronextamabOdronextamab for Relapsed and Refractory Large B-cell Lymphomas Before CAR-T

Sponsor:

University of Washington

Code:

NCT06784726

Conditions

Recurrent Diffuse Large B-Cell Lymphoma

Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

Recurrent Grade 3b Follicular Lymphoma

Recurrent High Grade B-Cell Lymphoma

Recurrent Primary Mediastinal Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Odronextamab

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Chimeric Antigen Receptor T-Cell Therapy

Study Details

Brief 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.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma

Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

Recurrent Grade 3b Follicular Lymphoma

Recurrent High Grade B-Cell Lymphoma

Recurrent Primary Mediastinal Large B-Cell Lymphoma

Study ID

NCT06784726

Start date

Sep 4, 2025

Status verified date

May, 2026

Completion date

Apr 11, 2033

Anticipated

Primary completion date

Apr 10, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Histologically confirmed large B cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, DLBCL arising from indolent lymphoma, follicular lymphoma (FL) grade 3B
Measurable disease, defined as at least one measurable lesion ≥ 15 mm on PET, CT, or magnetic resonance imaging (MRI) within one month of screening, according to the International Working Group consensus response evaluation criteria in lymphoma
Prior frontline therapy for large B cell lymphoma must have failed the patient, and criteria must be met for receiving commercial axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), or tisagenlecleucel (tisa-cel) per Food and Drug Administration (FDA) label
Age ≥ 18 years
Capable of understanding and providing a written informed consent
Prior treatment with an anti-CD20 antibody therapy
Eastern Cooperative Oncology Group performance status of 0-1; we allow enrollment of patients with a performance status of 2 if it is attributed to lymphoma per discretion of the treating physician or principal investigator (PI)
Creatinine clearance ≥ 45 mL/min calculated by Cockcroft-Gault equation
Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), except in patients with Gilbert's syndrome
Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x the ULN
Adequate pulmonary function, defined as ≤ grade 1 dyspnea and oxygen saturation (SpO2) ≥ 92% on room air
Adequate cardiac function, defined as left ventricular ejection fraction ≥ 50% and without evidence for pericardial effusion
Platelet count ≥ 75 x 10\^9 /L
Hemoglobin (Hg) level ≥ 9 g/dL
Absolute neutrophil count (ANC) ≥ 1 x 10\^9 /L
Patients with bone marrow involvement or splenic sequestration: Platelet count ≥ 25 x 10\^9 /L
Patients with bone marrow involvement or splenic sequestration: Hg ≥ 7.0 g/dL
Patients with bone marrow involvement or splenic sequestration: ANC ≥ 0.5 x 10\^9 /L
Negative serum pregnancy test within 2 days of initiating odronextamab for women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
Fertile male and WOCBP patients must be willing to use highly effective contraceptive methods from study recruitment to at least 6 months after the CAR T-cell infusion
Patients must not provide egg or sperm donation until at least 6 months after the completion of the last dose of Odron

Exclusion Criteria:

Detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases. Patients with a history of secondary central nervous system (CNS) lymphoma may be eligible provided that there has been no evidence of CNS disease from lymphoma for at least 3 months at the time of screening
History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
Standard anti-neoplastic chemotherapy (non-biologic) within 5-times the half-life or within 2 weeks, whichever is shorter, prior to first administration of study drug
Standard radiotherapy within 2 weeks of first administration of study drug
Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy, unless all the following are met: disease responded to prior bispecific therapy (CR or PR per Lugano criteria) and did not experience disease progression within 12 months of the last dose of prior bispecific therapy, and the tumor must still express CD20 (CD20 examination per standard of care \[SOC\])
Allogeneic stem cell transplantation
Any CAR-T cell therapy
Patients may not be receiving other investigational agents
Treatment with rituximab, alemtuzumab, or other investigational or commercial biologic agent within 2 weeks prior to first administration of study drug
Immunosuppressive therapy (other than biologic) within 2 weeks of first administration of study drug
Treatment with an investigational non-biologic agent within 2 weeks of first administration of study drug
History of allergic reactions attributed to compounds of similar chemical or biologic composition of study drug
History of hypersensitivity to any compound in the tetracycline antibiotics group
Concurrent active malignancy for which the patient is receiving systemic treatment, unless approved by PI
Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection
Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) and/or significant pulmonary disease (e.g., obstructive pulmonary disease and history of symptomatic bronchospasm)
Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent. A short course of corticosteroid for lymphoma disease control during screening is allowed
Infection with human immunodeficiency virus (unless viral load is undetectable and CD4 count ≥ 400) or chronic infection with hepatitis B virus or hepatitis C virus. Patients with hepatitis B (hepatitis B surface antigen positive \[HepBsAg+\]) with controlled infection were permitted upon consultation with the physician managing the infection
Known hypersensitivity to both allopurinol and rasburicase
Pregnant or breast-feeding women
Administration of live vaccination within 28 days of first administration of study drug

Study Design

Enrollment

27 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (odronextamab)

Patients receive odronextamab IV based on the following schedules:

Step-up dosing during cycle 1: 0.2 mg on C1D1, 0.5 mg on C1D2, 2 mg on C1D8 and C1D9, respectively, and 10 mg on C1D15 and C1D16, respectively (0.7/4/20 regimen).
Dosing during cycles 2-4: Odron will be given at 160 mg weekly.
Once every other week at 320 mg of remaining cycles.

Please see the Detailed Description for additional information.

Interventions

Odronextamab

Given IV

Biospecimen Collection

Undergo collection of blood and oral or rectal swab samples

Bone Marrow Aspiration

Undergo bone marrow aspiration

Bone Marrow Biopsy

Undergo bone marrow biopsy

Chimeric Antigen Receptor T-Cell Therapy

Undergo CAR-T cell therapy

Computed Tomography

Undergo PET/CT

Leukapheresis

Undergo leukapheresis

Lumbar Puncture

Undergo lumbar puncture

Positron Emission Tomography

Undergo PET/CT

Questionnaire Administration

Ancillary studies

Biopsy Procedure

Undergo tissue biopsy

Primary outcome measure

Failure to undergo leukapheresis [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Mengyang Di, MD, PhD

206-606-2519 mydi@fredhutch.org

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Mengyang Di, MD, PhD

206-606-2519 mydi@fredhutch.org

Principal Investigator:

Mengyang Di, MD, PhD

More Information

Sponsor

University of Washington

Last update posted

Aug 28, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Washington on 2026-08-28.