NCT06895473

Intrathecal Cytarabine, Methotrexate, and Hydrocortisone for the Prevention of High-Grade Chimeric Antigen Receptor T-Cell-Associated Neurotoxicity Syndrome

A Phase 2 Study of Prophylactic IT Chemotherapy to Prevent High-Grade Chimeric Antigen Receptor (CAR) T-Cell-Associated Neurotoxicity Syndrome

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well cytarabine (Ara-C), methotrexate, and hydrocortisone given between the spinal cord and the membranes that protect it (intrathecal \[IT\]) works in preventing high-grade immune effector-associated neurotoxicity syndrome (ICANS) in patients receiving chimeric antigen receptor (CAR) T-cell therapy. ICANS is a challenging complication of CAR T-cell therapy that causes neurological effects varying from mild headaches or temporary confusion to hallucinations, swelling in the brain, and seizures. Between 20%-70% of patients receiving CAR T-cell therapy show symptoms of neurotoxicity.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the efficacy of IT chemotherapy in the prevention of high grade ICANS. SECONDARY OBJECTIVES: I. To evaluate the efficacy of IT chemotherapy in the prevention of any grade ICANS. II. To evaluate safety of IT chemotherapy. III. To evaluate the effect of IT chemotherapy on corticosteroid use. IV. To evaluate the effect of IT chemotherapy on anakinra use. EXPLORATORY OBJECTIVES: I. To evaluate the effect of IT chemotherapy on time to ICANS onset. II. To evaluate the effect of IT chemotherapy on duration of ICANS. III. To evaluate the burden of treatment mediated serious adverse events (SAEs). OUTLINE: Patients receive cytarabine IT, methotrexate IT, and hydrocortisone IT over 3-5 minutes via lumbar puncture (LP) on day 4 post-standard of care (SOC) Axi-cel (Yescarta) or Brexu-cel (Tecartus) in the absence of unacceptable toxicity or development of ICANS. Patients who do not develop ICANS of any grade, also receive hydrocortisone IT on day 7 post SOC CAR T-cell therapy. Additionally, patients undergo cerebrospinal fluid (CSF) sample collection throughout the study. After completion of study treatment, patients are followed for up to 30 days.

Conditions

• Hematopoietic and Lymphatic System Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo CSF sample collection
DRUG	Cytarabine	Given IT
PROCEDURE	Lumbar Puncture	Undergo lumbar puncture
DRUG	Methotrexate	Given IT
DRUG	Therapeutic Hydrocortisone	Given IT

Timeline

• Start date: 2025-06-04
• Primary completion: 2027-04-30
• Completion: 2027-12-31
• First posted: 2025-03-26
• Last updated: 2026-01-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study