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

NCT04975555 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB-300007103
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cytokine Release Syndrome; ICANS; Lymphoma, Non-Hodgkin; Multiple Myeloma; Acute Lymphoblastic Leukemia

Keywords

Siltuximab; Chimeric Antigen Receptor T-cell Therapy; Cytokine release syndrome; Immune effector Cell associated Neurotoxicity Syndrome; Lymphoma; Multiple Myeloma; Acute lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline through 14 days

Secondary Outcomes (3)

• Participants with a response for Immune effector Cell Associated Neurotoxicity Syndrome (ICANS)

  Baseline through 28 days

• Participants experiencing adverse events from Siltuximab

  Baseline through 28 days

• Participants with response to CAR T-cell therapy

  Baseline through day 90

Study Arms (1)

Siltuximab

EXPERIMENTAL

Patients who experience CRS/ICANS will receive this treatment

Drug: Siltuximab

Interventions

Siltuximab DRUG

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.

Siltuximab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Cytokine Release Syndrome; Lymphoma, Non-Hodgkin; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma

Interventions

siltuximab

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia

Study Officials

• Amitkumar Mehta, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: July 23, 2021
• Study Start: November 15, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)