Pilot Study of Pre-emptive Anakinra for the Prevention of Severe Cytokine Release Syndrome in Children and Young Adults With B-Acute Lymphoblastic Leukemia Receiving Chimeric Antigen Receptor (CAR) T Cells
Overview
- Phase
- Phase 1
- Intervention
- Anakinra (Kineret®)
- Conditions
- B-Acute Lymphoblastic Leukemia
- Sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Rate of Severe CRS within 30 days of CAR T-cell infusion
- Status
- Not yet recruiting
- Last Updated
- 10 months ago
Overview
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.
Investigators
Kevin McNerney
Assistant Professor of Pediatrics
Ann & Robert H Lurie Children's Hospital of Chicago
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment Arm
Intervention: Anakinra (Kineret®)
Outcomes
Primary Outcomes
Rate of Severe CRS within 30 days of CAR T-cell infusion
Time Frame: 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 Outcomes
- Complete Remission Rate(28-35 days post CAR-T infusion)
- Overall and event-free survival(Up to 12 months post CAR-T infusion)
- CRS and ICANS Severity(Up to 12 months post CAR-T infusion)
- Immune effector cell-associated hematotoxicity (ICAHT) Severity(Up to 12 months post CAR-T infusion)
- Use of tocilizumab or steroids(Within 30 days post CAR T infusion)
- Infection severity(Within 30 days post CAR T infusion)
- Inflammatory markers and cell turnover(Within 30 days post CAR T infusion)
- Cell expansion and plasma cytokine profiles(Within 35 days post CAR T infusion)