Axicabtagene Ciloleucel CAR T-cells in Patients With Relapsed or Refractory Primary Mediastinal B-cell Lymphoma

Exclusion Criteria

• •1. Patients who received more than one prior line of systemic therapy
• •2. Prior CD19-targeted therapy
• •3. History of another primary malignancy that has not been in remission for at least 2 years (except for non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast)). A maintenance treatment is not allowed
• •4. History or presence of non-malignant CNS disorder, such as seizure disorder requiring anti-convulsive therapy, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months prior to enrollment.
• •• Secondary CNS involvement of PMBCL is not an exclusion criterion
• •5. History of acute or chronic active hepatitis B or C infection. If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing
• •6. Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a CD4 count \> 200 cells/μl
• •7. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal catheter). Dedicated venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
• •8. Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antimicrobials at the time of enrollment
• •9. Presence of cardiac atrial or ventricular lymphoma involvement
• •10. History of any one of the following cardiovascular conditions within the past 12 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• •11. History of any medical condition including but not limited to autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression and/or systemic disease modifying agents within the last year. Endocrine conditions that require maintenance with physiologic dose steroids are allowed
• •12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed
• •13. History of severe immediate hypersensitivity reaction to any of the agents used in this study, including aminoglycosides, cyclophosphamide, fludarabine or tocilizumab
• •14. Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
• •15. FCBP who are pregnant or breastfeeding
• •16. In the investigator's judgment, the patient is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
• •17. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness.
• •18. Simultaneously active participation in another clinical trial involving an IMP within 30 days prior to enrolment into this clinical trial
• •19. Patients with a physical or psychiatric condition which at the investigator's discretion may put the patient at risk, may confound the trial results, or may interfere with the patient's participation in this clinical trial
• •20. Known or persistent abuse of medication, drugs or alcohol
• •21. History of deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of enrollment
• •22. Primary immunodeficiency
• •23. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
• •24. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule