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
- Conditions
- B-Cell Non-Hodgkin Lymphoma
- Interventions
- Procedure: X-Ray ImagingProcedure: Positron Emission TomographyProcedure: Computed TomographyProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Lumbar PunctureProcedure: Biospecimen Collection
- Registration Number
- NCT04359784
- Lead Sponsor
- Fred Hutchinson Cancer Center
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
- 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
-
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
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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%
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Uncontrolled serious and active infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Prevention (anakinra, lisocabtagene maraleucel) Positron Emission Tomography 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. Prevention (anakinra, lisocabtagene maraleucel) Anakinra 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. Prevention (anakinra, lisocabtagene maraleucel) X-Ray Imaging 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. Prevention (anakinra, lisocabtagene maraleucel) Computed Tomography 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. Prevention (anakinra, lisocabtagene maraleucel) Bone Marrow Aspiration 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. Prevention (anakinra, lisocabtagene maraleucel) Bone Marrow Biopsy 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. Prevention (anakinra, lisocabtagene maraleucel) Lumbar Puncture 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. Prevention (anakinra, lisocabtagene maraleucel) Biospecimen Collection 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method Rate of hospitalization after liso-cel treatment Up to 28 days after liso-cel infusion 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.
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 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.
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.
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.
Trial Locations
- Locations (1)
Fred Hutch/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States