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

B-Cell Non-Hodgkin Lymphoma Clinical Trial

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 (B-NHL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04359784
• Other study ID #: RG1006866
• Secondary ID: NCI-2020-0186110
• Status: Recruiting
• Phase: Phase 2
• Start date: December 27, 2021
• Est. completion date: October 3, 2024

Study information

• Verified date: April 2024
• Source: Fred Hutchinson Cancer Center
• Contact: Cellular Immunotherapy Patient Care Coordinator
• Phone: 206-606-4668
• Email: immunotherapy[@]fredhutch.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: October 3, 2024
• Est. primary completion date: October 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-Cell Non-Hodgkin Lymphoma
• Cytokine Release Syndrome
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Neurotoxicity Syndromes

Intervention

Biological:
• Anakinra
Given IV (previously SC)

Procedure:
• X-Ray Imaging
Undergo x-ray
• Positron Emission Tomography
Undergo PET/CT
• Computed Tomography
Undergo PET/CT or CT
• Bone Marrow Aspiration
Undergo BMA
• Bone Marrow Biopsy
Undergo bone marrow biopsy
• Lumbar Puncture
Undergo lumbar puncture
• Biospecimen Collection
Undergo blood sample collection

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center	Swedish Orphan Biovitrum

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Rate of hospitalization after liso-cel treatment		Up to 28 days after liso-cel infusion
Secondary	Duration of hospitalization after liso-cel treatment		Up to 28 days after liso-cel infusion
Secondary	Corticosteroid usage after liso-cel treatment		Up to 28 days after liso-cel infusion
Secondary	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
Secondary	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