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

Study Overview
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Brief Summary
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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.

Detailed Description
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OUTLINE: Patients receive anakinra subcutaneously (SC) daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. After completion of lisocabtagene maraleucel infusion, patients are followed up periodically for up to 90 days.

Official Title
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Phase 2 Pilot Study to Evaluate Efficacy and Safety of Anakinra to Prevent CD19-Targeted CAR-T Cell-Related Cytokine Release Syndrome (CRS) and Neurotoxicity in Patients With B Cell Lymphoma

Conditions
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B-Cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: Anakinra


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention (anakinra, lisocabtagene maraleucel)<br>Patients receive anakinra SC daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. | Biological: Anakinra<br>* Given SC<br>* Other names: 143090-92-0;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 28 days after lisocabtagene maraleucel (liso-cel) infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRS grade | Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell. | Up to 28 days after liso-cel infusion | 
| Neurotoxicity grade | Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell. | Up to 28 days after liso-cel infusion | 
| Rate of hospitalization after liso-cel treatment |  | Up to 28 days after liso-cel infusion | 
| Duration of hospitalization after liso-cel treatment |  | Up to 28 days after liso-cel infusion | 
| Corticosteroid usage after liso-cel treatment |  | Up to 28 days after liso-cel infusion | 
| Disease response to liso-cel | Objective responses to the therapeutic regimen will be assessed based on institutional standard using physical examination, imaging (CT or PET-CT), and if necessary, bone marrow biopsies. | Approximately at 28 and 90 days after liso-cel infusion | 
| Adverse events (AEs) | Grade 3 or greater AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. | Up to 28 days after liso-cel infusion |