Study of Rituximab or Tocilizumab for Patients With Steroid-Dependent Immune-Related Adverse Events (irAEs)

Exclusion Criteria

• •Current participation in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• •Diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy other than steroids prior to the first dose of trial treatment
• •Treatment with a non-biologic immunosuppressive or immune-modulating drug (e.g. methotrexate, azathioprine, mycophenolate, cyclosporine, hydroxychloroquine, penicillamine) within 4 weeks prior to treatment. Note: Patients who previously received treatment with either rituximab or tocilizumab may receive treatment with the alternative agent after discussion with the treating physician and/or the principal investigator.
• •Treatment with other immune-modulating biologic agents within 4 weeks prior to treatment initiation.
• •History of anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins or any component of rituximab or tocilizumab History of allergic reactions attributed to compounds of similar chemical or biologic composition to either rituximab or tocilizumab.
• •History of human immunodeficiency virus (HIV) infection or other immunodeficiency.
• •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •History of chronic viral hepatitis, alcoholic or metabolic liver disease. Carriers of hepatitis B and patients with a history of hepatitis B infection or positive serology are excluded except in situations where the potential benefit is determined to justify the risk of possible hepatitis B reactivation, which can be fatal. Patients with positive serology should have viral DNA levels checked and a gastrointestinal consultation obtained. If treated with rituximab, such patients should be closely monitored for clinical and laboratory signs of active hepatitis B virus infection and for signs of hepatitis throughout their study participation.
• •Central nervous system (CNS) metastases, with the following exception:
• •Subjects who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids in the management of CNS disease (steroids for irAEs are allowed) at least 14 days prior to first dose of study drug. Note: Subjects with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
• •History of or current positive purified protein derivative tuberculin skin test (PPD) ( \>5mm induration, regardless of Bacille Calmette Guerin (BCG) vaccine administration), or positive QuantiFERON®-TB Gold In-Tube Test (QuantiFERON®), or historical chest x-ray unless completion of treatment has been documented for active tuberculosis (TB), latent TB (a positive test, a negative chest x-ray, and no symptoms or risk factors), unless one month of prophylaxis has been completed prior to inclusion, an indeterminate QuantiFERON® unless followed by a subsequent negative PPD or negative QuantiFERON® as well as a consultation with and clearance by local infectious disease (ID) department
• •If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •Transplanted organs (except corneas with transplant performed \>3 months prior to screening)
• •Active infection, including opportunistic infections, requiring systemic therapy within the past 2 weeks.
• •A deep space infection within the past 2 years (including, but not limited to meningitis, epiglottitis, endocarditis, septic arthritis, fasciitis, abdominal or pleural abscess, or osteomyelitis).
• •Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB)approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
• •New York Heart Association Classification III or IV heart disease
• •Breastfeeding is not permitted during treatment and for 6 months after the last dose of rituximab or 3 months after the last dose of tocilizumab.
• •Preexisting central nervous system demyelinating or seizure disorders
• •History of diverticulitis, diverticulosis requiring antibiotic treatment, or other symptomatic lower gastrointestinal (GI) conditions that might predispose to perforations.