Clinical trial · Interventional
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
NCT06895473CI-TRIAL-00116025recruitingPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Hematopoietic and Lymphatic System Neoplasm | Hematopoietic and Lymphatic System Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Biospecimen Collection | Procedure | — | UNRESOLVED |
| Cytarabine | Drug | Cytarabine | ALIAS |
| Lumbar Puncture | Procedure | — | UNRESOLVED |
| Methotrexate | Drug | Methotrexate | ALIAS |
| Therapeutic Hydrocortisone | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Supportive Care (cytarabine, methotrexate, hydrocortisone)
- description
- 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.
- interventionNames
- Procedure: Biospecimen Collection
- Drug: Cytarabine
- Procedure: Lumbar Puncture
- Drug: Methotrexate
- Drug: Therapeutic Hydrocortisone
Primary outcomes (1)
- measure
- Incidence of American Society for Transplantation and Cellular Therapy (ASTCT) ≥ grade 3 immune-effector cell associated neurotoxicity syndrome (ICANS)
- timeFrame
- From first dose of intrathecal (IT) chemotherapy (chimeric antigen receptor [CAR]-T day 4) to CAR-T day 30
- description
- Will be reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval will be reported.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available
No reference posted for this study.