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

NCT ID: NCT04359784

Last Updated: 2025-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-27
• Study Completion Date: 2024-12-23

Brief 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.

Detailed Description

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.

Conditions

B-Cell Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Prevention (anakinra, lisocabtagene maraleucel)

Patients receive anakinra IV (previously SC) 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, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.

Group Type: EXPERIMENTAL

Anakinra

Intervention Type: BIOLOGICAL

Given IV (previously SC)

X-Ray Imaging

Intervention Type: PROCEDURE

Undergo x-ray

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET/CT

Computed Tomography

Intervention Type: PROCEDURE

Undergo PET/CT or CT

Bone Marrow Aspiration

Intervention Type: PROCEDURE

Undergo BMA

Bone Marrow Biopsy

Intervention Type: PROCEDURE

Undergo bone marrow biopsy

Lumbar Puncture

Intervention Type: PROCEDURE

Undergo lumbar puncture

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Interventions

Anakinra

Given IV (previously SC)

Intervention Type: BIOLOGICAL

X-Ray Imaging

Undergo x-ray

Intervention Type: PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type: PROCEDURE

Computed Tomography

Undergo PET/CT or CT

Intervention Type: PROCEDURE

Bone Marrow Aspiration

Undergo BMA

Intervention Type: PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type: PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Other Intervention Names

Kinaret; Kineret; rIL-1ra; rIL1RN; 143090-92-0; Conventional X-Ray; Diagnostic Radiology; Medical Imaging; Radiographic Imaging; Medical Imaging; PET scan; CAT Scan; Computed Axial Tomography; CT scan; LP; spinal tap; Biological Sample Collection

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Jordan Gauthier

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jordan Gauthier

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2020-01861

Identifier Type: REGISTRY

Identifier Source: secondary_id

10373

Identifier Type: OTHER

Identifier Source: secondary_id

RG1006866

Identifier Type: -

Identifier Source: org_study_id