Using Anakinra to Prevent Severe Neurotoxicity in Lymphoma Patients After CAR T-Cell Therapy
IL-1 Receptor Antagonist to Prevent Severe Chimeric Antigen Receptor T-Cell Related Encephalopathy Syndrome
This study is testing if the drug anakinra can help prevent severe brain side effects in lymphoma patients receiving CAR T-cell therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Jonsson Comprehensive Cancer Center Academic / other |
| Drugs / interventions | alemtuzumab, pembrolizumab, ipilimumab, nivolumab, atezolizumab, CAR T, chemotherapy, chimeric antigen receptor, cyclophosphamide, fludarabine |
| Locations | 2 sites (Davis, California and 1 other locations) |
| Trial ID | NCT04205838 on ClinicalTrials.gov |
What this trial studies
This phase II trial investigates the effectiveness of anakinra in preventing severe chimeric antigen receptor T-cell-related encephalopathy syndrome (ICANS) in patients with recurrent or refractory large B-cell lymphoma undergoing CAR T-cell therapy. The study aims to determine the feasibility of participant accrual at a single site and estimate the efficacy of anakinra in reducing the incidence of ICANS. Secondary objectives include assessing the impact of anakinra on CAR T-cell therapy efficacy and evaluating the overall toxicity of the treatment. The trial will also explore changes in inflammatory markers and neurotoxicity duration.
Who should consider this trial
Good fit: Ideal candidates are patients with relapsed or refractory large B-cell lymphoma who have progressed on two prior lines of therapy and are eligible for CAR T-cell therapy.
Not a fit: Patients with primary CNS lymphoma or those who do not meet the eligibility criteria for CAR T-cell therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly reduce the risk of severe neurotoxicity in lymphoma patients receiving CAR T-cell therapy.
How similar studies have performed: While the use of anakinra in this context is novel, other studies have explored immunosuppressive therapies to mitigate neurotoxicity in CAR T-cell therapy, showing varying degrees of success.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patients with relapsed or refractory large B-cell lymphoma that has progressed on two prior lines of therapy, who meet the indication for the Food and Drug Administration (FDA)-approved therapy axicabtagene ciloleucel * Large B-cell lymphoma includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma * The above includes patients with progressive or stable disease as the best response to the most recent treatment regimen or disease progression within 12 months after autologous hematopoietic stem cell transplantation * Patients with central nervous system (CNS) involvement of large B-cell lymphoma that originated outside of the CNS will be included (not primary CNS lymphoma) * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 upper limit of normal * Total bilirubin =\< 2.0 mg/dL * Creatinine clearance \> 30 mL/min based on Cockcroft-Gault formula * Patients with human immunodeficiency virus (HIV) who have an undetectable viral load will be included * Deemed competent to make medical decisions Exclusion Criteria: * Patients who receive CAR T-cell therapy with a product other than axicabtagene ciloleucel * Primary CNS lymphoma * Transformed DLBCL from chronic lymphocytic leukemia (CLL) * Burkitt?s lymphoma * Bridging chemotherapy completed \< 7 days prior to CAR T-cell lymphodepleting chemotherapy * In patients who receive bridging chemotherapy, positron emission tomography (PET)-computed tomography (CT) or CT of chest, abdomen, pelvis was not done after bridging chemotherapy prior lympho-depleting therapy * Most recent PET-CT or CT of all known disease is sites done more than 6 weeks prior to CAR T-cell infusion * Any individual CNS tumor mass \> 2 cm * History of autologous hematopoietic stem cell transplantation administered less than 100 days prior to CAR T-cell infusion * History of allogeneic hematopoietic stem cell transplantation * Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis * Less than 3 half-lives elapsed since receiving immune checkpoint inhibitor (pembrolizumab, ipilimumab, nivolumab, atezolizumab, etc.) * Presence of uncontrolled fungal, bacterial, or viral infection that require intravenous (IV) antimicrobial treatment * History of autoimmune disease resulting in end-organ damage, or autoimmune disease requiring systemic immunosuppressants or disease-modifying antirheumatic drug (DMARDs) within the past 6 months * Hypersensitivity to E. Coli-derived proteins * Patients with HIV who have a detectable viral load * Pregnant or nursing * Fertile women who decline use of contraception during the study period
Where this trial is running
Davis, California and 1 other locations
- UC Davis Comprehensive Cancer Center — Davis, California, United States (Recruiting)
- UCLA / Jonsson Comprehensive Cancer Center — Los Angeles, California, United States (Recruiting)
Study contacts
- Principal investigator: John M Timmerman, MD — UCLA / Jonsson Comprehensive Cancer Center
- Study coordinator: Caspian Oliai, MD
- Email: coliai@mednet.ucla.edu
- Phone: 310-206-8477
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.