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Odronextamab for the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma Before and After Chimeric Antigen Receptor T-cell Therapy

RecruitingPhase 2Ages 18 Years - anyAllUniversity of California, Davis
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In plain words

What the trial is, and whether it could suit you

This phase II trial tests how well odronextamab works before and after standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapy in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR-T cell therapy is the SOC treatment most patients receive when other treatments have failed. CAR-T cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by

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📋 Eligibility rules (as published)
Inclusion Criteria: * Aged ≥ 18 at the time of consent * Patients must have histologically or cytologically confirmed relapsed/ refractory (R/R) diffuse large B-cell lymphoma (DLBCL); transformed follicular lymphoma patients are eligible * Patients must have failed at least 2 prior therapies * Life expectancy ≥ 3 months * Candidate for any Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cell therapy as per institutional guidelines * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%) * Leukocytes ≥ 2,500/µL * Absolute neutrophil count ≥ 1,000/µL or \> 500/µL for patients with bone marrow involvement * A participant may not have received granulocyte colony stimulating factor within 2 days prior to first dose of odronextamab in order to meet the absolute neutrophil count (ANC) eligibility criterion * Platelets ≥ 50,000/µL or ≥ 25,000/µL for patients with bone marrow involvement * A patient may not have received platelet transfusion therapy within 2 days prior to first dose of odronextamab in order to meet the platelet eligibility criterion * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) * NOTE: patients with known Gilbert disease who have serum bilirubin level ≤ 3 x institutional ULN may be enrolled. Patients with known Gilbert syndrome will be excluded if the total bilirubin value is \> 4 x ULN * Irrespective of the presence of lymphoma infiltration of the liver, a participant with an aspartate aminotransferase (AST) \> 3 x ULN and/or alanine aminotransferase (ALT) \> 3 x ULN concurrent with a total bilirubin \> 1.5 x ULN will be excluded * AST(serum glutamic oxaloacetic transaminase \[SGOT\])/ALT(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (AST and/or ALT ≤ 5 x ULN for patients with liver involvement) * Irrespective of the presence of lymphoma infiltration of the liver, a participant with an AST \> 3 x ULN and/or ALT \> 3 x ULN concurrent with a total bilirubin \> 1.5 x ULN will be excluded * Creatinine clearance ≥ 30 mL/min/1.73 m\^2 by Cockcroft-Gault * Hemoglobin ≥ 8 g/dL or ≥ 7 g/dL for patients with bone marrow involvement * NOTE: Growth factor or transfusion support is allowed as per treating physician's discretion * Alkaline phosphatase 2.5 x ULN (≤ 5 x ULN for patients with documented liver involvement or bone metastases) * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN * NOTE: This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose * Cardiac ejection fraction \> 50% by echocardiogram or multigated acquisition (MUGA) scan * Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance by Cockcroft Gault formula ≥ 50 mL/min * For participants infected with HIV: * No history of AIDS-defining conditions other than lymphoma or history of CD4+ T-cells below 200/mm\^3 prior to beginning combination antiretroviral therapy (ART) * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to ≥ 250/mm\^3 * At the time of study entry, the HIV viral load must be undetectable by standard laboratory assay * During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV+ status * No history of non-adherence to ART and willing to adhere to ART while on study * Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed * People with hepatitis B or C on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible * People of child-bearing potential and reproductive partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months (180 days) after the last dose of study agent. Egg and sperm donation is prohibited during the study and for 6 months after the last dose of study agent * Willing and able to provide informed consent Exclusion Criteria: * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she/they were to participate in the study or confounds the ability to interpret data from the study as determined by the study principal investigator (PI) or enrolling physician * Known involvement by primary central nervous system (CNS) lymphoma or known uncontrolled involvement by non-primary CNS non-Hodgkin lymphoma (NHL) at the time of study entry * Known history (within last 12 months) of or current relevant CNS pathology, such as: * Epilepsy, seizure, paresis, aphasia, apoplexy, severe brain injury, cerebellar disease, organic brain syndrome, psychosis, cerebrovascular stroke or * Evidence for presence of inflammatory lesions and/or vasculitis on cerebral magnetic resonance imaging (MRI) * Another active malignancy (aside from B-cell NHL) in the past 5 years, with the following exceptions: non-melanoma skin cancer that has undergone potentially curative therapy, in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent as per treating investigator * Evidence of any active infection (bacterial, viral, fungal, mycobacterial, parasitic, or other) at study enrollment or within 2 weeks of study enrollment, if requiring ongoing treatment and/or has the potential to cause disseminated disease or severe infection upon immunosuppression. There should be evidence that the infection has cleared or is well controlled by start of study therapy * Active COVID-19 infection * Uncontrolled infe
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What it tests

  • Chimeric Antigen Receptor T-Cell Therapy
  • Odronextamab
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Where

1 site
University of California Davis Comprehensive Cancer Center
Sacramento, United States
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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