Pre-emptive Anakinra for Cytokine Event Reduction

NCT ID: NCT06703216

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2030-02-28

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Group Type: EXPERIMENTAL

Anakinra (Kineret®)

Intervention Type: DRUG

Pre-emptive Anakinra at the initial onset of CRS.

Interventions

Anakinra (Kineret®)

Pre-emptive Anakinra at the initial onset of CRS.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Comorbid disease
• Other contraindications to allogeneic HSCT conditioning
• No suitable donor
• Prior HSCT
• Declines HSCT as the therapeutic option after documented discussion, with expected outcomes, about the role of HSCT with a HSCT physician
• Documentation of CD19+ tumor expression in the bone marrow, peripheral blood, cerebrospinal fluid (CSF), or tumor tissue by flow cytometry at relapse, or a recent sample in the case of refractory disease. If the patient has received CD19-directed Pre-emptive anakinra for severe CRS prevention therapy, the flow cytometry should be obtained after this therapy to show CD19 expression.
• Adequate organ function defined as:

• Alanine aminotransferase (ALT) < 500 U/L
• Bilirubin ≤2.0 mg/dL
• Minimum pulmonary reserve defined as ≤Grade 1 dyspnea, pulse oximetry >92% on room air; diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (corrected for anemia) if pulmonary function tests (PFTs) are clinically appropriate as determined by the treating investigator.
• Left ventricular shortening fraction ≥ 28% or ejection fraction ≥40% confirmed by echocardiography (ECHO), or adequate ventricular function documented by imaging or a cardiologist.
• Serum creatinine below the values in the below table, based on age/sex assigned at birth: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 1 to <2 0.6 0.6 2 to <6 0.8 0.8 6 to <10 1.0 1.0 10 to <13 1.2 1.2 13 to <16 1.5 1.4 ≥16 1.7 1.4
• Bone marrow disease burden of ≥5% or peripheral blasts within 2 weeks of the start of lymphodepleting chemotherapy
• Receiving commercially available tisagenlecleucel

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Kevin McNerney

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Countries

United States

Central Contacts

Kevin O McNerney, MD

Role: CONTACT

kmcnerney@luriechildrens.org

312-227-4090

Eric Brown

Role: CONTACT

errbrown@luriechildrens.org

312-227-4871

Facility Contacts

Kevin McNerney, MD

Role: primary

kmcnerney@luriechildrens.org

312-227-4859

Eric Brown

Role: backup

errbrown@luriechildrens.org

312-227-4871

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Other Identifiers

K12TR005104

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2024-7158

Identifier Type: -

Identifier Source: org_study_id