Siltuximab for Non-Hodgkin's Lymphoma

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Timothy Voorhees

Must not be taking: Steroids

Disqualifiers: Active CNS involvement, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 30 days

11 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Timothy J. Voorhees, MD, MSCR

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

Adults with CD19 positive non-Hodgkin lymphoma eligible for standard CAR-T cell therapy can join this trial. They must have certain blood and organ function levels, not be pregnant or breastfeeding, use contraception if of childbearing potential, and cannot have active central nervous system lymphoma or uncontrolled illnesses.

Inclusion Criteria

Aspartate aminotransferase (AST) =< 3.0 × ULN (obtained within 14 days prior to initiating study treatment)

I am eligible for a specific CAR-T cell therapy.

Hemoglobin >= 8.0 x 10^9/L (obtained within 14 days prior to initiating study treatment)

Exclusion Criteria

I do not have active brain conditions like epilepsy, severe strokes, or Parkinson's.

I had a severe reaction to my first siltuximab infusion.

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)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive siltuximab intravenously prior to CD19.CAR-T cell therapy and as clinically indicated on study

Up to 30 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and response rates

Up to 1 year

Regular follow-up visits

Treatment Details

Interventions

• Siltuximab

Trial Overview The trial is testing siltuximab's ability to prevent cytokine release syndrome (CRS) and neurotoxicity in patients undergoing CAR-T cell therapy. Siltuximab is an antibody that targets IL-6, a body chemical linked to these side effects.

Participant Groups

Group I: Treatment (siltuximab, biospecimen) Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

Timothy Voorhees

Lead Sponsor

Trials

3

Recruited

70+