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

Status: active

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. Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Methotrexate is in a class of medications called antimetabolites. It is also a type of antifolate. Methotrexate stops cells from using folic acid to make DNA and may kill cancer cells. Anti-inflammatory drugs, such as hydrocortisone, lower the body’s immune response and are used with other drugs in the treatment of some types of cancer. Giving IT cytarabine, methotrexate, and hydrocortisone may prevent high-grade ICANS in patients receiving CAR T-cell therapy.

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, 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

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 days 1 and 5 post-standard of care (SOC) CAR T-cell therapy in the absence of unacceptable toxicity or development of ICANS. Additionally, patients undergo cerebrospinal fluid (CSF) sample collection throughout the study.

After completion of study treatment, patients are followed for up to 30 days.

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

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Exclusion Criteria

United States

Oregon

Portland

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

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