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
Overview
- Phase
- Early Phase 1
- Intervention
- Tadekinig alfa (IL-18BP)
- Conditions
- CRS - Cytokine Release Syndrome
- Sponsor
- University of Pennsylvania
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Evaluate preliminary safety and feasibility of administering investigational rescue therapies for the treatment of CAR T cell related CRS and CRHLS.
- Status
- Recruiting
- Last Updated
- 2 months ago
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.
Investigators
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).
Arms & Interventions
Tadekinig alfa
* 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
Intervention: Tadekinig alfa (IL-18BP)
Outcomes
Primary Outcomes
Evaluate preliminary safety and feasibility of administering investigational rescue therapies for the treatment of CAR T cell related CRS and CRHLS.
Time Frame: 28 days
Type, frequency, and severity of AEs/SAEs determined to be related to the rescue therapy.