Intrathecal Cytarabine, Methotrexate, and Hydrocortisone for the Prevention of High-Grade Chimeric Antigen Receptor T-Cell-Associated Neurotoxicity Syndrome

Официальное название

A Phase 2 Study of Prophylactic IT Chemotherapy to Prevent High-Grade Chimeric Antigen Receptor (CAR) T-Cell-Associated Neurotoxicity Syndrome

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Biospecimen Collection
  Undergo CSF sample collection
• Препарат Cytarabine
  Given IT
• Процедура Lumbar Puncture
  Undergo lumbar puncture
• Препарат Methotrexate
  Given IT
• Препарат Therapeutic Hydrocortisone
  Given IT

Первичные конечные точки

• Incidence of American Society for Transplantation and Cellular Therapy (ASTCT) ≥ grade 3 immune-effector cell associated neurotoxicity syndrome (ICANS) [Срок оценки: From first dose of intrathecal (IT) chemotherapy (chimeric antigen receptor [CAR]-T day 4) to CAR-T day 30]

Вторичные конечные точки (4)

• Incidence of ASTCT any grade ICANS [Срок оценки: 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) [Срок оценки: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30]
• Mean (range) cumulative dose of corticosteroid use [Срок оценки: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30]
• Incidence of anakinra use [Срок оценки: From first dose of IT chemotherapy (CAR-T day 4) to CAR-T day 30]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

США · 1 центр

• OHSU Knight Cancer Institute — Portland

Идентификаторы

NCT: NCT06895473 · STUDY00028106 · NCI-2025-00937 · STUDY00028106

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗