Spinal injections of cytarabine, methotrexate, and hydrocortisone to prevent severe CAR T neurotoxicity
A Phase 2 Study of Prophylactic IT Chemotherapy to Prevent High-Grade Chimeric Antigen Receptor (CAR) T-Cell-Associated Neurotoxicity Syndrome
PHASE2 · OHSU Knight Cancer Institute · NCT06895473
This phase II test tries whether giving intrathecal cytarabine, methotrexate, and hydrocortisone around day 4 (with a day 7 hydrocortisone if no symptoms) can prevent severe neurotoxicity in adults receiving Yescarta or Tecartus CAR T-cell therapy.
Quick facts
| Phase | PHASE2 |
|---|---|
| Study type | Interventional |
| Enrollment | 26 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | OHSU Knight Cancer Institute (other) |
| Drugs / interventions | CAR-T, chemotherapy, CAR T, chimeric antigen receptor, methotrexate |
| Locations | 1 site (Portland, Oregon) |
| Trial ID | NCT06895473 on ClinicalTrials.gov |
What this trial studies
This open-label phase II trial delivers a single intrathecal dose of cytarabine, methotrexate, and hydrocortisone via lumbar puncture on day 4 after standard-of-care axi-cel (Yescarta) or brexu-cel (Tecartus), with an additional intrathecal hydrocortisone on day 7 for participants who have not developed ICANS. Cerebrospinal fluid (CSF) samples are collected throughout the study to monitor biological effects, and patients are followed for up to 30 days after treatment. The primary outcome is prevention of high-grade ICANS, with secondary outcomes including prevention of any-grade ICANS, safety, and effects on corticosteroid and anakinra use. Exploratory analyses examine time to ICANS onset, duration of ICANS, and treatment-related serious adverse event burden.
Who should consider this trial
Good fit: Adults aged 18 or older receiving inpatient standard-of-care Yescarta or Tecartus at the enrolling center who can provide informed consent and have no contraindication to lumbar puncture or intrathecal chemotherapy are ideal candidates.
Not a fit: Patients who already develop ICANS before the planned day 4 lumbar puncture, those with contraindications to lumbar puncture or intrathecal therapy, or those treated at other centers are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could reduce the number of patients who develop severe CAR T–related neurotoxicity and lower the need for high-dose steroids and intensive supportive care.
How similar studies have performed: Intrathecal chemotherapy as a preventive strategy for CAR T–associated neurotoxicity is largely novel, while prior work has mostly focused on systemic steroids, tocilizumab, and cytokine-targeted therapies rather than intrathecal prophylaxis.
Eligibility criteria
Show full inclusion / exclusion criteria
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 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
Where this trial is running
Portland, Oregon
- OHSU Knight Cancer Institute — Portland, Oregon, United States (RECRUITING)
Study contacts
- Principal investigator: Stephen E Spurgeon — OHSU Knight Cancer Institute
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Hematopoietic and Lymphatic System Neoplasm