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

NCT04359784 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1006866NCI-2020-0186110373
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• CRS Grade

  Up to 28 days after liso-cel infusion

• ICANS Grade

  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

Study Arms (1)

Prevention (anakinra, lisocabtagene maraleucel)

EXPERIMENTAL

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.

Biological: Anakinra; Procedure: X-Ray Imaging; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Lumbar Puncture; Procedure: Biospecimen Collection

Interventions

Anakinra BIOLOGICAL

Given IV (previously SC)

Also known as: Kinaret, Kineret, rIL-1ra, rIL1RN, 143090-92-0

Prevention (anakinra, lisocabtagene maraleucel)

X-Ray Imaging PROCEDURE

Undergo x-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, Radiographic Imaging

Prevention (anakinra, lisocabtagene maraleucel)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, PET scan

Prevention (anakinra, lisocabtagene maraleucel)

Computed Tomography PROCEDURE

Undergo PET/CT or CT

Also known as: CAT Scan, Computed Axial Tomography, CT scan

Prevention (anakinra, lisocabtagene maraleucel)

Bone Marrow Aspiration PROCEDURE

Undergo BMA

Prevention (anakinra, lisocabtagene maraleucel)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Prevention (anakinra, lisocabtagene maraleucel)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, spinal tap

Prevention (anakinra, lisocabtagene maraleucel)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Prevention (anakinra, lisocabtagene maraleucel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Swedish Orphan Biovitrum: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6; X-Rays; Phantoms, Imaging; Magnetic Resonance Spectroscopy; Spinal Puncture

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative

Results Point of Contact

• Title: Jordan Gauthier
• Organization: Fred Hutchinson Cancer Center

jgauthier@fredhutch.org

206-667-2713

Study Officials

• Jordan Gauthier

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 24, 2020
• Study Start: December 27, 2021
• Primary Completion: October 1, 2024
• Study Completion: December 23, 2024
• Last Updated: October 23, 2025
• Results First Posted: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)