Cytokine Release SyndromePhase 2NCT04975555
Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to CAR-T Cell Therapy
A Phase 2 study testing Siltuximab in people with Cytokine Release Syndrome and ICANS, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytokine Release Syndrome, ICANS, Lymphoma, Non-Hodgkin
- What is being tested?
- Siltuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2021to 20 Jan 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: 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 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.
Read the detailed description
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.
- Conditions
- Cytokine Release Syndrome, ICANS, Lymphoma, Non-Hodgkin, Multiple Myeloma, Acute Lymphoblastic Leukemia
- Being tested
- Siltuximab
- Keywords
- Siltuximab, Chimeric Antigen Receptor T-cell Therapy, Cytokine release syndrome, Immune effector Cell associated Neurotoxicity Syndrome, Lymphoma, Multiple Myeloma, Acute lymphoblastic Leukemia
- Medical subject headings
- Cytokine Release Syndrome, Lymphoma, Non-Hodgkin, Multiple Myeloma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SiltuximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Siltuximab | Experimental | Patients who experience CRS/ICANS will receive this treatment Receives: Drug: Siltuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline through 14 days
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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]
Measured: Baseline through day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2021
- Study start15 Nov 2021
- Primary completion20 Jan 2026
- Study completion20 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cytokine Release SyndromeStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Recordati Rare Diseases Inc
- Responsible party
- Principal investigator, Aditi Saha, MD, University of Alabama at Birmingham
- Investigators
- Amitkumar Mehta, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04975555
- Sponsor's protocol ID
- IRB-300007103
- Other IDs
- University of Alabama
- Status last verified
- Jun 2026
- First submitted
- 5 Jul 2021
- Last updated
- 27 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: To Be determined