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

NCT ID: NCT06784726

Last Updated: 2025-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-04

Study Completion Date

2033-04-11

Brief Summary

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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

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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.

Conditions

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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 Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Refractory Grade 3b Follicular Lymphoma Refractory High Grade B-Cell Lymphoma Refractory Primary Mediastinal Large B-Cell Lymphoma Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Odronextamab

Intervention Type BIOLOGICAL

Given IV

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood and oral or rectal swab samples

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Chimeric Antigen Receptor T-Cell Therapy

Intervention Type BIOLOGICAL

Undergo CAR-T cell therapy

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Leukapheresis

Intervention Type PROCEDURE

Undergo leukapheresis

Lumbar Puncture

Intervention Type PROCEDURE

Undergo lumbar puncture

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Biopsy

Intervention Type PROCEDURE

Undergo tissue biopsy

Interventions

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Odronextamab

Given IV

Intervention Type BIOLOGICAL

Biospecimen Collection

Undergo collection of blood and oral or rectal swab samples

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Chimeric Antigen Receptor T-Cell Therapy

Undergo CAR-T cell therapy

Intervention Type BIOLOGICAL

Computed Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Leukapheresis

Undergo leukapheresis

Intervention Type PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Biopsy

Undergo tissue biopsy

Intervention Type PROCEDURE

Other Intervention Names

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REGN1979 Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody REGN1979 WHO 11035 Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow Biopsy, Bone Marrow CAR T Infusion CAR T Therapy CAR T-cell Therapy Chimeric Antigen Receptor T-cell Infusion CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography Leukocyte Adsorptive Apheresis Leukocytopheresis Therapeutic Leukopheresis White Blood Cell Reduction Apheresis LP Spinal Tap Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Bx

Eligibility Criteria

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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 ≥ 50 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
* 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
* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mengyang Di, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Mengyang Di, MD, PhD

Role: CONTACT

206-606-2509

Facility Contacts

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Mengyang Di, MD, PhD

Role: primary

206-606-2509

Other Identifiers

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NCI-2024-10534

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020747

Identifier Type: OTHER

Identifier Source: secondary_id

RG1124641

Identifier Type: -

Identifier Source: org_study_id

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