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

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04359784
Collaborator
National Cancer Institute (NCI) (NIH), Swedish Orphan Biovitrum (Industry)
25
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26.2
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Anakinra
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
25 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
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
Actual Study Start Date :
Dec 27, 2021
Anticipated Primary Completion Date :
Mar 3, 2024
Anticipated Study Completion Date :
Mar 3, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Prevention (anakinra, lisocabtagene maraleucel)

Patients receive anakinra SC daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0.

Biological: Anakinra
Given SC
Other Names:
  • Kinaret
  • Kineret
  • rIL-1ra
  • rIL1RN
  • 143090-92-0
  • Outcome Measures

    Primary Outcome Measures

    1. Absence of any grade cytokine release syndrome (CRS) [Up to 28 days after lisocabtagene maraleucel (liso-cel) infusion]

      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.

    Secondary Outcome Measures

    1. CRS grade [Up to 28 days after liso-cel infusion]

      Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

    2. Neurotoxicity grade [Up to 28 days after liso-cel infusion]

      Graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.

    3. Rate of hospitalization after liso-cel treatment [Up to 28 days after liso-cel infusion]

    4. Duration of hospitalization after liso-cel treatment [Up to 28 days after liso-cel infusion]

    5. Corticosteroid usage after liso-cel treatment [Up to 28 days after liso-cel infusion]

    6. Disease response to liso-cel [Approximately at 28 and 90 days after liso-cel infusion]

      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.

    7. Adverse events (AEs) [Up to 28 days after liso-cel infusion]

      Grade 3 or greater AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fred Hutch/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • National Cancer Institute (NCI)
    • Swedish Orphan Biovitrum

    Investigators

    • Principal Investigator: Jordan Gauthier, Fred Hutch/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT04359784
    Other Study ID Numbers:
    • RG1006866
    • NCI-2020-01861
    • P30CA015704
    • 10373
    First Posted:
    Apr 24, 2020
    Last Update Posted:
    Mar 22, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 22, 2022