This study will evaluate the use of siltuximab to decrease the severity of cytokine release syndrome (CRS) and immune effector cell-associated neurological syndrome (ICANS) in patients who will receive chimeric antigen receptor (CAR) T-cell therapy for the treatment of hematological malignancies.
Patients eligible to receive CAR T-cell therapy for FDA-approved indications in hematological malignancies will be enrolled in this study on the day of CAR T-cell infusion. Patients will be followed until they develop grade 1 or higher CRS and/or ICANS. On developing these syndromes, siltuximab will be administered with close monitoring and follow-up for resolution of symptoms. If symptoms continue to worsen, then an additional dose of siltuximab will be given. If the symptoms leading to CRS do not resolve, then rescue tocilizumab will be administered. The study's primary endpoint is to assess the response rate of siltuximab in the resolution of CRS within 14 days. The study's secondary endpoint is to assess the response rate of siltuximab in the resolution of ICANS, the safety of siltuximab, and the overall response rate of CAR T-cell therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Siltuximab is administered at the dose of 11mg/kg via intravenous infusion over 1 hour. If no resolution of CRS is achieved then a repeat dose of siltuximab at the dose of 11mg/kg via intravenous infusion over 1 hour will be given.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Participants with a complete response for cytokine release syndrome (CRS)
Participants who achieve a resolution of CRS. Resolution of CRS is defined as absence of symptoms leading to diagnosis of CRS for 24 hours.
Time frame: Baseline through 14 days
Participants with a response for Immune effector Cell Associated Neurotoxicity Syndrome (ICANS)
Participants who achieve a resolution or improvement in their ICANS. Complete response or partial response for ICANS is defined as either complete disappearance or decrease in the grade of severity as measured by ASTCT Consensus Grading for ICANS. The ASTCT grade is from 1 to 5 for ICANS with 1 being mild symptoms and 5 being severe symptoms.
Time frame: Baseline through 28 days
Participants experiencing adverse events from Siltuximab
All Adverse Events (AE's) will be reported and evaluated using National Cancer Institute's Common Terminology Criteria (CTCAE) v5.0.
Time frame: Baseline through 28 days
Participants with response to CAR T-cell therapy
This will be measured by using specific criteria's for Lymphoma, Multiple Myeloma or Acute Lymphoblastic Leukemia (ALL) \[Based on the patients diagnosis\]
Time frame: Baseline through day 90
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