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.
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
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
Presence of a posterior fossa mass
Single group
Biospecimen Collection
Procedure/SurgeryUndergo CSF sample collection
Cytarabine
DrugGiven IT
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Methotrexate
DrugGiven IT
Therapeutic Hydrocortisone
DrugGiven IT
Incidence of American Society for Transplantation and Cellular Therapy (ASTCT) ≥ grade 3 immune-effector cell associated neurotoxicity syndrome (ICANS)
Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
Incidence of ASTCT any grade ICANS
Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
Incidence of lumbar puncture/IT treatment related adverse events (AEs) and serious adverse events (SAEs)
Will be reported using the safety set. AEs will be tabulated by the Medical Dictionary for Regulatory Activities version (v) 21.1. preferred term and system organ class and a preferred term. The severity of the AE will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (CTCAE) v 5.0. Descriptive statistics using the safety evaluable population, will be used to report on all on-study AEs, grade 3-4 AEs, treatment-related AEs, grade 3-4 treatment-related AEs, SAEs, treatment-related SAEs, and AEs leading to discontinuation per CTCAE v 5.0. Grade 3-4 laboratory abnormalities will be summarized using worst grade NCI CTCAE v 5.0 criteria.
Mean (range) cumulative dose of corticosteroid use
Will be reported using the efficacy set. The cumulative dose will be calculated as the sum of all corticosteroid administered over the study period, expressed in milligrams (mg) of prednisone-equivalent.
Incidence of anakinra use
Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
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OHSU Knight Cancer Institute
Lead sponsor
Oregon Health and Science University
Collaborator
American Society of Clinical Oncology
Collaborator
