Tadekinig Alfa (IL-18BP) Rescue Therapy for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome

HLH Clinical Trial

Official title:

Pilot, Open-Label Study Evaluating the Safety and Feasibility of Using Rescue Therapies for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05306080
• Other study ID #: UPCC 01422
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 17, 2022
• Est. completion date: April 2025

Study information

• Verified date: February 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a pilot, open-label study to assess the safety and feasibility of using investigational drug(s) as rescue therapies for CAR T cell related CRS and HLH-like syndrome (CRHLS).

Description:

This pilot, open-label trial will allow for co-enrollment of subjects participating in University of Pennsylvania-Sponsored, CCI-Initiated CAR T cell studies. As utilization of this investigational drug may be required emergently in the event of qualifying safety events post CAR T cell infusion, subjects may be consented/enrolled at the time they receive an investigational CAR T cell product. If/when use of this investigational drug is deemed clinically necessary, rescue therapy may then be initiated. Cohort 1: Will allow for the use of Tadekinig alfa, an interleukin-18 binding protein that binds and neutralizes IL-18. IL-18 is a key mediator in systemic inflammatory conditions such as MAS/HLH, which may contribute to the severity of CAR T cell-related cytokine release syndrome (CRS) and HLH-like syndrome (CRHLS) and impact response to standard therapy. In addition, subjects experiencing other IL-18 driven toxicity post CAR T cell therapy which is non-responsive to conventional treatment may also receive rescue therapy with Tadekinig alfa as per clinical discretion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: April 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed, written informed consent

2. Male or female patients age = 18 years

3. Have been co-enrolled in a University of Pennsylvania-Sponsored, CCI-Initiated CAR T cell clinical trial.

4. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol

Exclusion Criteria:

1. Pregnant or nursing (lactating) women.

2. Known hypersensitivity to the active substance or one of the excipients of the investigational product(s).

Related Conditions & MeSH terms

• Cytokine Release Syndrome
• HLH
• Syndrome

Intervention

Drug:
• Tadekinig alfa (IL-18BP)
Tadekinig alfa will be administered via subcutaneous injection. The site of subcutaneous injection should be rotated to avoid injection site reactions; e.g. the outside of the thighs, arms, and the various quadrants of the anterior abdominal wall. Injection #1/Day 1: o Loading dose of 4 mg/kg; Maximum dose of 350 mg. Repeat Injection(s): 2 mg/kg/injection; Maximum dose of 160 mg/injection. Missed doses will not be made up. Injection #2/Day 3: Approximately 48 hours (+/- 5 hours) after receipt of the 1st injection. Injection #3/Day 5: Approximately 48 hours (+/- 5 hours) after receipt of the 2nd injection. Continued Dosing (Optional): Approximately q48-72 hours; If the subject is responsive to initial therapy, but has ongoing symptoms of CRS/CRHLS.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate preliminary safety and feasibility of administering investigational rescue therapies for the treatment of CAR T cell related CRS and CRHLS.	Type, frequency, and severity of AEs/SAEs determined to be related to the rescue therapy.	28 days