Siltuximab for the Treatment of Cytokine Release Syndrome and Neurological Toxicity Related to Chimeric Antigen Receptor T-cell Therapy in Hematological Malignancies

Inclusion Criteria

• Patients who are planned to receive chimeric antigen receptor T-cell therapy as per the United States Food and Drug Agency (USFDA) approved indications for * Diffuse large B-cell lymphoma (DLBCL), * Mantle cell lymphoma (MCL), * Follicular lymphoma (FL), * Primary mediastinal large B-cell lymphoma (PMBCL), * High grade B-cell lymphoma, * DLBCL arising from follicular lymphoma. * Multiple myeloma * B-cell precursor acute lymphoblastic leukemia
• Patients with hepatitis C virus (HCV) can be included if they have completed therapy for hepatitis C with undetectable HCV ribonucleic acid (RNA) viral load
• Patients with hepatitis B can be included if they are on suppressive therapy for hepatitis B infection and with no detectable viral load
• Bilirubin =< 2mg/dL (7 days to 30 days before planned CAR T-cell infusion)
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) (7 days to 30 days before planned CAR T-cell infusion)
• Calculated creatinine clearance (crcl) > 30ml/min using Cockroft-Gault, based on actual weight (7 days to 30 days before planned CAR T-cell infusion)
• Absolute neutrophil count (ANC) >= 1,000/mL (7 days to 30 days before planned CAR T-cell infusion)
• Hemoglobin (Hgb) > 8 (7 days to 30 days before planned CAR T-cell infusion)
• Platelet count >= 50,000/mL (7 days to 30 days before planned CAR T-cell infusion)
• Patients able to tolerate washout periods for therapies as defined below prior to CAR T-cell infusion * Systemic therapy: Washout period is 2 weeks prior to CAR T-cell infusion * Radiation therapy: Washout period is 1 week prior to CAR T-cell infusion * Corticosteroids: Washout period is 5 days prior to CAR T-cell infusion
• Age >= 18 years of age
• A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 months after infusion of siltuximab
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
• Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of investigational product and being admitted, when required, for at least 24 hours during investigational product administration

Exclusion Criteria

• Subjects requiring ongoing daily corticosteroid therapy at a dose of > 10 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable
• Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the principal investigator (PI)
• Pregnant women are excluded from this study
• Evidence of ongoing systemic bacterial, or fungal or viral infection, except localized fungal infection of skin or nails
• Patients with ongoing or past human immunodeficiency virus (HIV) infections