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

Study Overview
=================
Brief 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).

Detailed 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.

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

Conditions
-----------------
CRS - Cytokine Release Syndrome, HLH

Intervention / Treatment
-----------------
* Drug: Tadekinig alfa (IL-18BP)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed, written informed consent Male or female patients age ≥ 18 years Have been co-enrolled in a University of Pennsylvania-Sponsored, CCI-Initiated CAR T cell clinical trial. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Exclusion Criteria: Pregnant or nursing (lactating) women. Known hypersensitivity to the active substance or one of the excipients of the investigational product(s).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadekinig alfa<br>Injection #1/Day 1: As clinically indicated in accordance with Figure 1.1-1. Repeat Injection(s): 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. Retreatment (Optional): May be considered | Drug: Tadekinig alfa (IL-18BP)<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |