A Phase 2 Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxicity

Exclusion Criteria

• •History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
• •History of Richter's transformation of CLL
• •Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion
• •History of allogeneic stem cell transplantation
• •Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for re-treatment
• •Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
• •History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
• •Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
• •History of HIV infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines.
• •Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
• •Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
• •History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• •Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
• •History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• •Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)
• •Primary immunodeficiency
• •History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
• •Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
• •History of severe immediate hypersensitivity reaction to any of the agents used in this study
• •Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen
• •Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
• •Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of axicabtagene ciloleucel
• •In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
• •History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years