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

Fred Hutchinson Cancer Center27 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

B-Cell Non-Hodgkin Lymphoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Absence of Any Grade Cytokine Release Syndrome (CRS)

Will assess the efficacy of anakinra in preventing the occurrence of any grade CRS using the Bayesian optimal phase 2 design. Assessed based on the ASTCT Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

Time frame: Up to 28 days after lisocabtagene maraleucel (liso-cel) infusion

Secondary Outcomes

CRS Grade

CRS severity was graded per American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria (Lee et al, Biol Blood Marrow Transplant, 2019) based on the presence and severity of fever, hypotension, and hypoxia: grade 1, fever ≥38°C without hypotension or hypoxia; grade 2, hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen; grade 3, hypotension requiring a single vasopressor or hypoxia requiring high-flow oxygen; grade 4, life-threatening hypotension requiring multiple vasopressors and/or hypoxia requiring positive-pressure ventilation; grade 5, death.