Tests emapalumab to prevent CAR-T treatment side effects in lymphoma

Who can take part

• Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Or adult patients with 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 per Lugano at time of screening
• Age 18 or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Adequate renal, hepatic, pulmonary and cardiac function defined as:; ANC ≥1000/uL; Platelet count ≥50,000/uL; Absolute lymphocyte count ≥100/uL; Creatinine clearance (as estimated by Cockcroft Gault or CKD-EPI) ≥ 30 mL/min; Serum ALT/AST ≤2.5 per institutional ULN; Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome; Cardiac ejection fraction ≥ 40%, no clinically significant pericardial effusion, and no clinically significant ECG findings; 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

Who cannot take part

• Autologous stem cell transplant within 6 weeks of planned CAR-T infusion
• No evidence of active CNS disease regardless of prior CNS history
• Receipt of a BCG vaccine within 12 weeks prior to Screening
• Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screeing
• Participants who are receiving any other investigational agents for this condition
• 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 allogeneic stem cell transplantation
• Presence of uncontrolled fungal, bacterial, viral, or other infection at time of screening
• Known history of 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; Patients should also be negative for latent Tb, CMV (NAT), EBV (NAT) and adenovirus (NAT) by PCR testing
• History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage within 6 months of enrollment
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• History of symptomatic pulmonary embolism within 3 months of enrollment; ongoing anticoagulation is allowed if beyond 3 months
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
• History of allergic reactions or severe immediate hypersensitivity reaction to any of the agents used in this study or compounds of similar chemical or biologic composition
• History of autoimmune disease requiring ongoing systemic immunosuppression. Steroids are allowed up to 5mg predinosine-equivalent for adrenal insufficiency
• Patients anticipated to require canakinumab, JAK inhibitors, TNF inhibitors, and tocilizumab for non-CAR-T management of baseline autoimmune/inflammatory disease at the time of emapalumab initiation
• Females who are pregnant or breastfeeding or female or male participants who are not willing to practice birth control from the time of consent through 6 months after the completion of CAR-T
• 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