RecruitingPhase 2NCT06895473

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

Sponsor

OHSU Knight Cancer Institute

Enrollment

26 participants

Start Date

Jun 4, 2025

Study Type

INTERVENTIONAL

Conditions

Hematopoietic and Lymphatic System Neoplasm

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

Written informed consent. Participant or legally authorized representative (LAR) must provide written informed consent prior to any study-specific procedures or interventions
Age ≥ 18 years. All genders, races, and ethnic groups will be included
Must be receiving SOC Yescarta® or Tecartus® in the inpatient setting
Agree to adhere to institutional guidelines for contraception during the first 30 days post CAR-T
Rationale for eligibility criteria based on contraception and pregnancy (both participants and partners of a sperm-producing participant): It shall be known to all participants that the effects of CAR-T or IT chemotherapy on the developing human fetus are unknown. For this reason, persons of reproductive potential must agree to use adequate contraception. Should a participant or participant's sexual partner become pregnant or suspect a pregnancy while participating in this study, the individual should inform their treating physician immediately
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Platelet count > 50,000/mm\^3 (μL)
Adequate coagulation tests including international normalized ratio (INR) < 1.6 and fibrinogen > 100

Exclusion Criteria12

Active/concurrent diagnosis of any central nervous system (CNS) hematologic malignancy
History or presence of CNS disorder such as poorly controlled seizure disorder (seizure within the 12 months), transverse myelitis, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
Known history of hypersensitivity to IT chemotherapy
Subject has a contraindication to LP including:
Presence of a posterior fossa mass
Skin infection near puncture site
Uncorrected bleeding diathesis
Suspicion of increased intracranial pressure
Acute spinal cord trauma
Subject is receiving an antiplatelet and/or anticoagulant that cannot be held prior to LP according to best available evidence
Known bleeding disorders
Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the participant inappropriate for study participation or would put the participant at risk