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

Launched by UNIVERSITY OF WASHINGTON · Jan 14, 2025

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ClinConnect Summary

This clinical trial is studying a new treatment called odronextamab for patients with certain types of large B-cell lymphomas that have come back after treatment or did not respond to previous therapies. The goal is to see if giving odronextamab before a specific type of therapy known as CAR-T cell therapy can help control the cancer better and improve the chances of successful treatment. Odronextamab works by targeting cancer cells and helping the body’s immune system fight against them.

To participate in this trial, you need to be at least 18 years old and have been diagnosed with specific types of large B-cell lymphoma that have not responded to earlier treatments. You should also have measurable disease, meaning that your doctor can see at least one tumor that is a certain size on imaging tests like a CT scan. Participants can expect to receive odronextamab as a treatment to help manage their condition before undergoing CAR-T therapy. It's essential to discuss with your doctor to see if you meet the eligibility criteria and understand the potential risks and benefits of joining this study.

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Eligibility criteria

• 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