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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
26
Undergo CSF sample collection
Given IT
Undergo lumbar puncture
Given IT
Given IT
OHSU Knight Cancer Institute
Portland, Oregon, United States
RECRUITINGIncidence 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.
Time frame: From first dose of intrathecal (IT) chemotherapy (chimeric antigen receptor [CAR]-T day 4) to CAR-T day 30
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.
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
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.
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
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.
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
Incidence of anakinra use
Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
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