RECRUITING

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

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Conditions

Recurrent 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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Odronextamab for Relapsed/Refractory Large B-cell Lymphomas Before Definitive Lymphoma-Directed Therapies

Quick Facts

Study Start:2025-07-15
Study Completion:2033-04-11
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06784726

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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
  2. * 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
  3. * 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
  4. * Age ≥ 18 years
  5. * Capable of understanding and providing a written informed consent
  6. * Prior treatment with an anti-CD20 antibody therapy
  7. * 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)
  8. * Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault equation
  9. * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), except in patients with Gilbert's syndrome
  10. * Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x the ULN
  11. * Adequate pulmonary function, defined as ≤ grade 1 dyspnea and oxygen saturation (SpO2) ≥ 92% on room air
  12. * Adequate cardiac function, defined as left ventricular ejection fraction ≥ 50% and without evidence for pericardial effusion
  13. * Platelet count ≥ 75 x 10\^9 /L
  14. * Hemoglobin (Hg) level ≥ 9 g/dL
  15. * Absolute neutrophil count (ANC) ≥ 1 x 10\^9 /L
  16. * Patients with bone marrow involvement or splenic sequestration: Platelet count ≥ 25 x 10\^9 /L
  17. * Patients with bone marrow involvement or splenic sequestration: Hg ≥ 7.0 g/dL
  18. * Patients with bone marrow involvement or splenic sequestration: ANC ≥ 0.5 x 10\^9 /L
  19. * 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
  20. * 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
  21. * Patients must not provide egg or sperm donation until at least 6 months after the completion of the last dose of Odron
  1. * Detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases
  2. * History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
  3. * 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
  4. * Standard radiotherapy within 2 weeks of first administration of study drug
  5. * Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy
  6. * Allogeneic stem cell transplantation
  7. * Any CAR-T cell therapy
  8. * Patients may not be receiving other investigational agents
  9. * Treatment with rituximab, alemtuzumab, or other investigational or commercial biologic agent within 2 weeks prior to first administration of study drug
  10. * Immunosuppressive therapy (other than biologic) within 2 weeks of first administration of study drug
  11. * Treatment with an investigational non-biologic agent within 2 weeks of first administration of study drug
  12. * History of allergic reactions attributed to compounds of similar chemical or biologic composition of study drug
  13. * History of hypersensitivity to any compound in the tetracycline antibiotics group
  14. * Concurrent active malignancy for which the patient is receiving systemic treatment, unless approved by PI
  15. * Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection
  16. * 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)
  17. * 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
  18. * 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
  19. * Known hypersensitivity to both allopurinol and rasburicase
  20. * Pregnant or breast-feeding women
  21. * Administration of live vaccination within 28 days of first administration of study drug

Contacts and Locations

Study Contact

Mengyang Di, MD, PhD
CONTACT
206-606-2509
mydi@fredhutch.org

Principal Investigator

Mengyang Di, MD, PhD
PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
United States

Collaborators and Investigators

Sponsor: University of Washington

  • Mengyang Di, MD, PhD, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-15
Study Completion Date2033-04-11

Study Record Updates

Study Start Date2025-07-15
Study Completion Date2033-04-11

Terms related to this study

Additional Relevant MeSH Terms

  • 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