Pre-emptive Anakinra for Cytokine Event Reduction

Phase 1

Not yet recruiting

• Conditions: B-Acute Lymphoblastic Leukemia; CAR-T Cell Therapy; Cytokine Release Syndrome; Immune Effector Cell Associated Neurotoxicity Syndrome; Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome
• Interventions: Drug: Anakinra (Kineret®)

• Registration Number: NCT06703216
• Lead Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Brief Summary

Objectives: The primary objective of this study will be to evaluate the impact of pre-emptive use of anakinra on the rate of severe cytokine release syndrome (CRS) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for B-acute lymphoblastic leukemia (B-ALL) in children and young adults.

Patient Population: Children and young adults \<25 years of age undergoing CAR T-cell therapy for B-ALL with bone marrow disease burden of ≥5% involvement or detectable peripheral blasts within 2 weeks of the initiation of lymphodepleting chemotherapy.

Study Design: This is a pilot single arm study. The investigators will inquire into the efficacy and safety of using anakinra pre-emptively to reduce the rate of severe CRS in patients with \>/=5% bone marrow blasts or lymphoblasts in the peripheral blood.

Treatment Plan:

This is a single arm unblinded study in which patients will receive anakinra, 2.5 mg/kg (max 100mg), IV every 12 hours starting at the onset of persistent fever (fever \>38.5⁰ C x 2 occurrences separated by at least 4 hours in a 24 hour period). If there is persistence or progression of CRS, anakinra frequency will be increased to 2.5mg/kg IV (max 100mg), every 6 hours. Anakinra will be continued until 48 hours after resolution of CRS and ICANS, and at least 7 days post-CAR T infusion. If dose and frequency of anakinra is increased, the increased dose of anakinra will be continued until 48 hours after resolution of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) and at least 7 days post-CAR T infusion. For CRS worsening beyond dose escalation of anakinra, CRS will be managed as per standard of care management. Participants will be followed for 12 months following enrollment in the study and disease evaluations will be performed as per routine clinical care following CAR T-cell therapy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-18
• Study First Submitted QC: 2024-11-21
• Study First Posted: 2024-11-25
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-30
• Last Update Posted: 2024-12-31
• Study Start: 2025-01-15
• Primary Completion: 2029-08-31
• Study Completion: 2030-02-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Anakinra (Kineret®)	-

Primary Outcome Measures

Name	Time	Method
Rate of Severe CRS within 30 days of CAR T-cell infusion	30 days of CAR-T infusion	The rate of severe CRS, grade ≥3 CRS, as defined by the American Society of Transplantation and Cellular Therapy (ASTCT) consensus guidelines. Participants will have CRS grading each day of hospitalization and every clinical visit within the first 30 days of CAR T-cell infusion.

Secondary Outcome Measures

Name	Time	Method
Infection severity	Within 30 days post CAR T infusion	Rate of severe infections (as defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade \>/=3)
Complete Remission Rate	28-35 days post CAR-T infusion	1. Complete Remission Rate at day 28-35 post-CAR-T
Overall and event-free survival	Up to 12 months post CAR-T infusion	6- and 12-month overall and event-free survival
CRS and ICANS Severity	Up to 12 months post CAR-T infusion	Rate and any grade of CRS, any grade ICANS, severe (grade \>/=3) ICANS, any grade IEC-HS
Immune effector cell-associated hematotoxicity (ICAHT) Severity	Up to 12 months post CAR-T infusion	Rate of any grade and grade \>/=3 ICAHT as defined by European Hematology Association (EHA)/European Society for Blood and Marrow Transplantation (EBMT) guidelines
Use of tocilizumab or steroids	Within 30 days post CAR T infusion	Use of tocilizumab and steroids in the treatment of CRS, ICANS, or Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS)
Inflammatory markers and cell turnover	Within 30 days post CAR T infusion	Inflammatory markers (C-reactive protein, ferritin) and markers of cell turnover (lactate dehydrogenase and uric acid)
Cell expansion and plasma cytokine profiles	Within 35 days post CAR T infusion	CAR T-cell expansion and plasma cytokine profiles

Trial Locations

Locations (1)

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States