A Phase 2 Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxicity
This research study is studying the combination of anakinra and axicabtagene ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities with relapsed or refractory Non-Hodgkin lymphoma (NHL). * Relapsed NHL is the condition of returned Non-Hodgkin lymphoma. * Refractory NHL is the condition of previous treatment resistant Non-Hodgkin lymphoma. * Cytokine Release Syndrome (CRS) is a group of side effect symptoms that can include nausea, headache, rapid heartbeat, shortness of breath, kidney damage, and rash. * Neurologic toxicity is nervous system disorder characterized by confusion This research study involves two drugs: * Anakinra * Axicabtagene Ciloleucel.
• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
• At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma 1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy however steroids only require a 7-day washout. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc).
• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)
• Age 18 or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• ANC ≥1000/uL
• Platelet count ≥75,000/uL
• Absolute lymphocyte count ≥100/uL
• Adequate renal, hepatic, pulmonary and cardiac function defined as:
‣ Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
⁃ Serum ALT/AST ≤2.5 ULN
⁃ Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome.
⁃ Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion, and no clinically significant ECG findings
⁃ No clinically significant pleural effusion
⁃ Baseline oxygen saturation \>92% on room air
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) Ability to understand and the willingness to sign a written informed consent document.