Intrathecal Cytarabine, Methotrexate, and Hydrocortisone for the Prevention of High-Grade Chimeric Antigen Receptor T-Cell-Associated Neurotoxicity Syndrome
Hematopoietic and Lymphatic System Neoplasm
What this study involves
The registry says this study is recruiting. Individual locations may have different availability.
- Study type
- Interventional
- Phase
- Phase 2
- Age range
- 18 years - Not specified
- Sex eligible
- All sexes
- Healthy volunteers
- Not accepted
- Participants
- 26 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
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.
Read the full 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.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
Inclusion Criteria:
- 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 Criteria:
- Active/concurrent diagnosis of any central nervous system (CNS) hematologic malignancy
- History or presence of CNS disorder such as seizure disorder, 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
Treatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Not applicable
- Masking
- No masking
Supportive Care (cytarabine, methotrexate, hydrocortisone)
Patients receive cytarabine IT, methotrexate IT, and hydrocortisone IT over 3-5 minutes via LP on day 4 post-SOC CAR T-cell therapy 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 CSF sample collection throughout the study.
Procedure: Biospecimen Collection · Drug: Cytarabine · Procedure: Lumbar Puncture · Drug: Methotrexate · Drug: Therapeutic Hydrocortisone
Biospecimen Collection PROCEDURE
Undergo CSF sample collection
Cytarabine DRUG
Given IT
Lumbar Puncture PROCEDURE
Undergo lumbar puncture
Methotrexate DRUG
Given IT
Therapeutic Hydrocortisone DRUG
Given IT
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Incidence of American Society for Transplantation and Cellular Therapy (ASTCT) ≥ grade 3 immune-effector cell associated neurotoxicity syndrome (ICANS)
Time frame: From first dose of intrathecal (IT) chemotherapy (chimeric antigen receptor [CAR]-T day 4) to CAR-T day 30
Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
Secondary measures
Incidence of ASTCT any grade ICANS
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
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 mediated adverse events (AEs) and serious adverse events (SAEs)
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
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
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
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
Time frame: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30
Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.
1 locations
OHSU Knight Cancer InstitutePortland, Oregon, United StatesRecruiting
Study team and timeline
- Lead sponsor
- OHSU Knight Cancer Institute
- Study start
- Jun 4, 2025 Actual
- Primary completion
- Apr 30, 2027 Estimated
- Study completion
- Dec 31, 2027 Estimated
- First posted
- Mar 26, 2025 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
No central contact is listed. Check the locations and the official record.
Official study title
A Phase 2 Study of Prophylactic IT Chemotherapy to Prevent High-Grade Chimeric Antigen Receptor (CAR) T-Cell-Associated Neurotoxicity Syndrome
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 12, 2026 · Last registry update: Nov 10, 2026