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

ConditionsRecurrent Diffuse Large B-Cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent Grade 3b Follicular LymphomaRecurrent High Grade B-Cell LymphomaRecurrent Primary Mediastinal Large B-Cell LymphomaRecurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory Grade 3b Follicular LymphomaRefractory High Grade B-Cell LymphomaRefractory Primary Mediastinal Large B-Cell LymphomaRefractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Washington

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Odronextamab

    Biological/Vaccine

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood and oral or rectal swab samples

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Chimeric Antigen Receptor T-Cell Therapy

    Biological/Vaccine

    Undergo CAR-T cell therapy

  • Computed Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Leukapheresis

    Procedure/Surgery

    Undergo leukapheresis

  • Lumbar Puncture

    Procedure/Surgery

    Undergo lumbar puncture

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tissue biopsy

Treatment groups

27 Participants
are divided into 1 treatment group
Group A: Treatment (odronextamab)Experimental treatment 11 interventions

Trial outcomes

Primary outcomes

1

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 outcomes

1

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
2

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
3

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
4

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

Other outcomes

Sponsors and contacts

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

University of Washington

Lead sponsor

Regeneron Pharmaceuticals

Collaborator

Source ClinicalTrials.gov
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