Evaluating Siltuximab for Treating Severe Reactions from CAR-T Cell Therapy
A Phase II Pilot Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to Chimeric Antigen Receptor T-Cell Therapy (CAR-T) in Hematological Malignancies
This study is testing if siltuximab can help people with severe reactions from CAR-T cell therapy feel better by reducing symptoms like cytokine release syndrome and neurotoxicity.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Alabama at Birmingham Academic / other |
| Drugs / interventions | siltuximab, CAR T, chimeric antigen receptor, Radiation, prednisone, tocilizumab |
| Locations | 1 site (Birmingham, Alabama) |
| Trial ID | NCT04975555 on ClinicalTrials.gov |
What this trial studies
This study evaluates the effectiveness of siltuximab in reducing the severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients undergoing CAR T-cell therapy for hematological malignancies. Eligible patients will receive siltuximab upon developing grade 1 or higher CRS and/or ICANS, with close monitoring for symptom resolution. The primary endpoint is the response rate of siltuximab in resolving CRS within 14 days, while secondary endpoints include the resolution of ICANS and the overall response rate of CAR T-cell therapy. The study aims to provide insights into the safety and efficacy of siltuximab in this context.
Who should consider this trial
Good fit: Ideal candidates are patients scheduled to receive CAR T-cell therapy for specific hematological malignancies such as lymphoma and multiple myeloma.
Not a fit: Patients who are not receiving CAR T-cell therapy or those with uncontrolled infections may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve patient outcomes by effectively managing severe side effects associated with CAR T-cell therapy.
How similar studies have performed: Other studies have explored similar interventions, but the specific use of siltuximab in this context is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patients who are planned to receive chimeric antigen receptor T-cell therapy as per the United States Food and Drug Agency (USFDA) approved indications for Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma (MCL), Follicular lymphoma (FL), Primary mediastinal large B-cell lymphoma (PMBCL), High grade B-cell lymphoma, DLBCL arising from follicular lymphoma, Multiple myeloma and B-cell precursor acute lymphoblastic leukemia * Patients with hepatitis C virus (HCV) can be included if they have completed therapy for hepatitis C with undetectable HCV RNA viral load. * Patients with Hepatitis B can be included if they are on suppressive therapy for hepatitis B infection and with no detectable viral load. * Adequate organ function as defined below unless attributed to disease involvement.Acceptable window for assessing adequate organ function is 7 days to 30 days before planned CAR T-cell infusion with day 0 as the planned day of CAR T-cell infusion.Adequate liver function (bilirubin \< 2mg/dL, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<3 x ULN), adequate kidney function (crcl \> 30ml/min using Cockcroft-Gault, based on actual weight) and adequate hematological parameters (Absolute neutrophil count ≥ 1,000/µL, Hemoglobin \> 8, Platelet Count ≥ 50,000/ µL) * Patients able to tolerate washout periods for therapies prior to CAR T-cell infusion. Systemic therapy: Washout period is 2 weeks prior to CAR T-cell infusion. Radiation therapy: Washout period is 1 week prior to CAR T-cell infusion. Corticosteroids: The washout period is 5 days prior to CAR T-cell infusion. * A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial. * For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 months after infusion of siltuximab. * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner * Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of the investigational product and being admitted, when required, for at least 24 hours during investigational product administration. Exclusion Criteria: * Subjects requiring ongoing daily corticosteroid therapy at a dose of \> 10 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) * Pregnant women are excluded from this study. * Evidence of ongoing systemic bacterial, or fungal or viral infection, except localized fungal infection of skin or nails. * Patients with ongoing or past HIV infection.
Where this trial is running
Birmingham, Alabama
- University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)
Study contacts
- Principal investigator: Mayur S Narkhede — University of Alabama at Birmingham
- Study coordinator: Mayur Narkhede
- Email: msnarkhede@uabmc.edu
- Phone: 205-934-2248
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.