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

Last updated: January 24, 2025
Sponsor: University of Alabama at Birmingham
Overall Status: Active - Recruiting

Phase

2

Condition

Multiple Myeloma

Bone Neoplasm

Platelet Disorders

Treatment

Siltuximab

Clinical Study ID

NCT04975555
IRB-300007103
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients who are planned to receive chimeric antigen receptor T-cell therapy as perthe United States Food and Drug Agency (USFDA) approved indications for Diffuselarge B-cell lymphoma (DLBCL), Mantle cell lymphoma (MCL), Follicular lymphoma (FL),Primary mediastinal large B-cell lymphoma (PMBCL), High grade B-cell lymphoma, DLBCLarising from follicular lymphoma, Multiple myeloma and B-cell precursor acutelymphoblastic leukemia

  • Patients with hepatitis C virus (HCV) can be included if they have completed therapyfor hepatitis C with undetectable HCV RNA viral load.

  • Patients with Hepatitis B can be included if they are on suppressive therapy forhepatitis B infection and with no detectable viral load.

  • Adequate organ function as defined below unless attributed to diseaseinvolvement.Acceptable window for assessing adequate organ function is 7 days to 30days before planned CAR T-cell infusion with day 0 as the planned day of CAR T-cellinfusion.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 adequatehematological 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-cellinfusion. 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 ofchildbearing potential prior to enrolling on this trial.

  • For females of reproductive potential: use of highly effective contraception for atleast 1 month prior to screening and agreement to use such a method during studyparticipation and for an additional 4 months after infusion of siltuximab.

  • For males of reproductive potential: use of condoms or other methods to ensureeffective contraception with partner

  • Willing and able to participate in all required evaluations and procedures in thisstudy protocol including receiving intravenous administration of the investigationalproduct and being admitted, when required, for at least 24 hours duringinvestigational product administration.

Exclusion

Exclusion Criteria:

  • Subjects requiring ongoing daily corticosteroid therapy at a dose of > 10 mg ofprednisone per day (or equivalent). Pulsed corticosteroid use for disease control isacceptable.

  • Active autoimmune disease requiring immunosuppressive therapy is excluded unlessdiscussed with the principal investigator (PI)

  • Pregnant women are excluded from this study.

  • Evidence of ongoing systemic bacterial, or fungal or viral infection, exceptlocalized fungal infection of skin or nails.

  • Patients with ongoing or past HIV infection.

Study Design

Total Participants: 30
Treatment Group(s): 1
Primary Treatment: Siltuximab
Phase: 2
Study Start date:
November 15, 2021
Estimated Completion Date:
December 31, 2027

Study 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.

Connect with a study center

  • University of Alabama at Birmingham

    Birmingham, Alabama 35294
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.