anakinra for the prevention of cytokine release syndrome and neurotoxicity in patients with b-cell non-hodgkin lymphoma receiving cd19-targeted car-t cell therapy

Conditions: B-Cell Non-Hodgkin Lymphoma

Summary: this phase ii trial studies how well anakinra works in decreasing the occurrence of cytokine release syndrome (crs) and damage to the nerves (neurotoxicity) in patients with b-cell non-hodgkin lymphoma who are receiving cd-19 targeted chimeric antigen receptor t-cell (car-t) therapy. car-t cell therapy may be complicated by two potentially life-threatening side effects: crs and neurotoxicity. anakinra is a drug typically used to treat rheumatoid arthritis, but may also help in preventing car-t cell-related cytokine release syndrome and neurotoxicity.

outline: patients receive anakinra intravenously (iv) \[previously subcutaneously (sc) for some patients\] over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. patients should also undergo at screening an x-ray, positron emission tomography/computed tomography (pet/ct) or ct, bone marrow aspirate (bma) and biopsy (if clinically indicated), and lumbar puncture (if clinically indicated), and at follow-up as clinically indicated. patients also undergo blood sample collection on study. after completion of lisocabtagene maraleucel infusion, patients are followed up periodically for up to 90 days.

Eligibility criteria:
inclusion criteria: * subjects must be 18 years of age or older * karnofsky performance status of \>= 60% * patients with b-cell non-hodgkin lymphoma (b-nhl) and eligible for treatment with liso-cel. patients treated with non-conforming (out-of-specification) liso-cell may remain on study. * negative serum pregnancy test within 2 weeks of enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year * fertile male and female subjects must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of anakinra * ability to understand and provide informed consent exclusion criteria: * subjects requiring ongoing daily corticosteroid therapy at a dose of \> 15 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) * known hypersensitivity to escherichia € coli-derived proteins, anakinra, or to any component of the product * major organ dysfunction defined as: * serum creatinine \> 2.5 mg/dl * significant hepatic dysfunction (alanine aminotransferase (alt) and aspartate aminotransferase (ast) \> 5x upper limit of normal; bilirubin \> 3.0 mg/dl) unless due to malignancy or gilbert's syndrome in the opinion of the pi or designee * subjects with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. those with a forced expiratory volume in 1 second (fev1) of \< 50% of predicted or diffusion capacity of the lung for carbon monoxide (dlco) (corrected) \< 40% will be excluded * significant cardiovascular abnormalities as defined by any one of the following: new york heart association (nyha) class iii or iv congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of \< 35% * uncontrolled serious and active infection