Siltuximab for the Prevention of CAR T Cell Related Cytokine Release Syndrome in Patients With CD19 Positive Non-Hodgkin Lymphoma

NCT05665725 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-22031NCI-2022-10248
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety and side effects of siltuximab in preventing CAR T cell therapy related cytokine release syndrome in patients with CD19 positive non-Hodgkin lymphoma. Several of the major complications of CD19 directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) include cytokine release syndrome (CRS, a complication of a highly active immune system seen with some cancer treatments including CD19.CAR-T cell therapy) and immune effector cell therapy associated neurotoxicity (ICANS, neurologic complications related to an activated immune system seen with immunotherapy and CD19.CAR-T cell therapy). Siltuximab is a chimeric (having parts of different origins) murine (from mice) antibody that binds directly to IL-6 (a cytokine/ body chemical causing toxicities) and allows for its clearance. IL-6 is known to increase in a patient's blood after CD19.CAR-T cell infusion and has been associated with development of CRS and ICANS. Giving siltuximab prior to CD19.CAR-T cell therapy may help reduce CRS and/or ICANS after therapy.

Conditions

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Frequency and nature of adverse events associated with siltuximab prophylaxis prior to CD19 directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) cell therapy

  Adverse events (AEs) will be described and classified per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 guidelines. The maximum grade of each type of toxicity will be extracted for each patient, and frequency counts will be tabulated to determine toxicity patterns, especially for grade 3 or above adverse events. The AE data associated with prophylaxis will be summarize for every patient: for patients receiving siltuximab only as prophylaxis, all AEs occur during the 30-day dose limiting toxicity observation period will be considered; for patients receiving siltuximab both as prophylaxis and as treatment, only the AEs occur before the treatment start will be considered for the primary endpoint.

  Up to 30 days after the last infusion of siltuximab

Secondary Outcomes (7)

• Frequency and nature of adverse events associated with siltuximab treatment of cytokine release syndrome (CRS) and/or immune effector cell associated neurotoxicity syndrome (ICANS)

  Up to 30 days after the last infusion of siltuximab

• Incidence of all grade CRS and grade >= 3 CRS

  Up to 30 days after the last infusion of siltuximab

• Incidence of all grade ICANS and grade >= 3 ICANS

  Up to 30 days after the last infusion of siltuximab

• Percentage of participants who achieve resolution of CRS

  At 24 hours from treatment

• Objective response rate (complete response [CR] + partial response [PR])

  At day 30 following CD19.CAR-T cell therapy

Study Arms (1)

Treatment (siltuximab, biospecimen)

EXPERIMENTAL

Patients receive siltuximab IV prior to CE19.CAR-T cell therapy and as clinically indicated on study. Patients undergo CT scan or PET scan throughout the trial. Patients also undergo blood sample collection during screening and on study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Biological: Siltuximab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (siltuximab, biospecimen)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (siltuximab, biospecimen)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (siltuximab, biospecimen)

Siltuximab BIOLOGICAL

Given IV

Also known as: Anti-IL-6 Chimeric Monoclonal Antibody, cCLB8, CNTO 328, CNTO-328, Sylvant

Treatment (siltuximab, biospecimen)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• Age \>= 18 years at the time of consent
• Diagnosis of non-Hodgkin lymphoma
• Eligible for standard of care CD19.CAR-T cell therapy including axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel and lisocabtagene maraleucel)
• Subjects with hepatitis B virus (HBV) can be included if on suppressive antiviral therapy and have no detectable viral load
• Subjects with hepatitis C virus (HCV) can be included if HCV ribonucleic acid (RNA) viral load is undetected
• Measurable disease of \> 1.5 cm in diameter and/or bone marrow involvement
• White blood cell count \>= 1.0 x 10\^9/L (obtained within 14 days prior to initiating study treatment)
• Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Hemoglobin \>= 8.0 x 10\^9/L (obtained within 14 days prior to initiating study treatment)
• Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Platelets \>= 50 x 10\^9/L (obtained within 14 days prior to initiating study treatment)
• Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Creatinine =\< 2.0 x upper limit of normal (ULN) (obtained within 14 days prior to initiating study treatment)
• Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

You may not qualify if:

• Subjects requiring daily corticosteroids at a dose \> 10mg of prednisone per day (orequivalent). Pulsed steroids for disease control are acceptable
• Subjects who are planned to receive prophylactic steroids for mitigating CRS/ICANS before, during, or after CD19.CAR-T infusion
• Active central nervous system or meningeal involvement by lymphoma. Subjects with symptoms of possible central nervous system (CNS) disease should undergo CNS workup with magnetic resonance imaging (MRI) brain and diagnostic lumbar puncture prior to enrollment on this study. Subjects with a history of CNS or meningeal involvement must be in a documented remission by cerebrospinal spinal fluid (CSF) evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration
• Patients with history of clinically relevant and active CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease
• Human immunodeficiency virus (HIV) seropositivity
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drugs)
• Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non compensated hypertension (systolic blood pressure \>= 180mmHg or diastolic blood pressure \>= 120mmHg)
• FOR SILTUXIMAB TREATMENT OF CRS/ICANS: Subjects with CRS and no evidence of ICANS who require dexamethasone (or any steroid) due to severity of CRS as determined by the investigators
• FOR SILTUXIMAB TREATMENT OF CRS/ICANS: Prior history of a dose limiting toxicity (see section 6.5) due to siltuximab infusion according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria v5.0
• SECOND SILTUXIMAB TREATMENT DOSE FOR CRS/ICANS: Subjects with CRS and no evidence of ICANS who require dexamethasone (or any steroid) due to severity of CRS as determined by the investigators
• SECOND SILTUXIMAB TREATMENT DOSE FOR CRS/ICANS: Prior history of a dose limiting toxicity due to siltuximab infusion according to NCI-CTCAE criteria v5.0

Sponsors & Collaborators

• Timothy Voorhees: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; siltuximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Timothy J Voorhees, MD, MSCR

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: December 27, 2022
• Study Start: January 31, 2023
• Primary Completion: September 27, 2023
• Study Completion: September 6, 2024
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)