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

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 (B-NHL)

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.

Study Overview

• Status: Recruiting
• Conditions: B-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Procedure: Lumbar Puncture; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Procedure: X-Ray Imaging; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Bone Marrow Aspiration; Biological: Anakinra

Detailed Description

OUTLINE:

Patients receive anakinra intravenously (IV) [previously subcutaneously (SC) for some patients] 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
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cellular Immunotherapy Patient Care Coordinator; Phone Number: 206-606-4668; Email: immunotherapy@fredhutch.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Jordan Gauthier
      • Contact: Cellular Immunotherapy Patient Care Coordinator; Phone Number: 206-606-4668; Email: immunotherapy@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prevention (anakinra, lisocabtagene maraleucel); Patients receive anakinra IV (previously SC) 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.

Procedure: Lumbar Puncture; Undergo lumbar puncture; Other Names: LP; spinal tap; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: PET scan; Medical Imaging; Procedure: X-Ray Imaging; Undergo x-ray; Other Names: Conventional X-Ray; Diagnostic Radiology; Radiographic Imaging; Medical Imaging; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Procedure: Computed Tomography; Undergo PET/CT or CT; Other Names: CAT Scan; Computed Axial Tomography; CT scan; Procedure: Bone Marrow Aspiration; Undergo BMA; Biological: Anakinra; Given IV (previously SC); Other Names: Kinaret; Kineret; rIL-1ra; rIL1RN; 143090-92-0

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: Swedish Orphan Biovitrum
• Investigators: Principal Investigator: Jordan Gauthier, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2021
• Primary Completion (Estimated): October 3, 2024
• Study Completion (Estimated): October 3, 2024

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Poisoning; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neurotoxicity Syndromes; Cytokine Release Syndrome; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: RG1006866; NCI-2020-01861 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 10373 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No