Intrathecal Cytarabine and Hydrocortisone for the Early Treatment of ICANS in Patients Undergoing CAR T Therapy for Non Hodgkin Lymphoma

NCT07763210 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: VICCCTT26-01
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to reduce the duration of ICANS and incidence of G3 or great ICANS in participants who receive axi-cel. The main questions the study aims to answer are: Efficacy of IT therapy to reduce high-grade ICANS in participants who receive axi-cel in NHL compared to historical experience. This phase II trial tests how well giving intrathecal (IT) cytarabine and hydrocortisone works for the early treatment of immune effector cell associated neurotoxicity syndrome (ICANS) in patients undergoing chimeric antigen response (CAR) t cell therapy for the treatment of non Hodgkin Lymphoma that has come back after a period of improvement (recurrent) or that has not responded o previous treatment (refractory). CAR T-cell therapy can sometimes cause an overactive immune response and inflammation. This can cause a side effect called ICANS that affects the rain and may lead to symptoms such as confusion, difficulty speaking, or other neurological problems. Giving cytarabine and hydrocortisone directly into the fluid around the brain and spinal cord (called intrathecal treatment) may help lower the body's immune response and reduce inflammation. Giving IT cytarabine and hydrocortisone may be effective for early treatment of CANS in patients undergoing CAR T cell therapy for relapsed or refractory non Hodgkin Lymphoma.

Conditions

Non-hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma

Keywords

relapsed; refractory

Outcome Measures

Primary Outcomes (2)

• Efficacy of IT therapy to reduce high-grade ICANS in participants who receive axi-cel in NHL compared to historical experience

  Incidence of \> Grade 3 ICANS after IT therapy in subjects with grade 1-2 ICANS

  From first IT therapy through 14 days from last IT therapy (Up to 3 months)

• Progression free survival

  Will be analyzed using the Kaplan-Meier method to estimate the survival distribution.

  From the day of CAR T therapy infusion to objective disease progression, initiation of any non-protocol anti-lymphoma therapy, or death from any cause, up to 3 months.

Secondary Outcomes (6)

• Impact of IT therapy on CAR T toxicities

  From first IT therapy through 14 days from last IT therapy (Up to 3 months)

• Adverse events from IT therapy

  From first IT therapy tthrough 14 days from last IT therapy (Up to 3 months)

• Feasibility of IT therapy

  time from onset of ICANS to administration of first IT therapy

• Impact of IT therapy on SOC management of CRS and ICANS

  time from CAR T infusion (day 0) through Post treatment Day +28

• Impact of IT therapy on disease outcome

  time from CAR T infusion (day 0) through Post treatment Day +90

Study Arms (2)

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone

EXPERIMENTAL

Drugs will be given at onset of grade 1/2 ICANS after Axi-cel or Brexu-cel

Drug: Therapeutic Hydrocortisone; Drug: Cytarabine; Drug: Dexamethasone; Drug: Methylprednisolone; Drug: Cyclophosphamide; Biological: Axicabtagene Ciloleucel; Biological: Brexucabtagene Autoleucel

Prophylactic corticosteroids with Dexamethasone

ACTIVE COMPARATOR

Drugs will be given at onset of grade 1/2 ICANS after Axi-cel or Brexu-cel

Drug: Dexamethasone; Drug: Cyclophosphamide; Biological: Axicabtagene Ciloleucel; Biological: Brexucabtagene Autoleucel

Interventions

Dexamethasone DRUG

IV 10mg

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone; Prophylactic corticosteroids with Dexamethasone

Methylprednisolone DRUG

1g daily until adverse events resolves

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone

Therapeutic Hydrocortisone DRUG

100 mg IT with onset of grade 1/2 ICANS

Also known as: (11beta)-11,17,21-Trihydroxypregn-4-ene-3,20-dione, Dermacort

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone

Cytarabine DRUG

100 mg IT with onset of grade 1/2 ICANS

Also known as: ARA-cell, Beta-Cytosine Arabinoside

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone

Cyclophosphamide DRUG

Given as standard of care

Also known as: (-)-Cyclophosphamide, 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone; Prophylactic corticosteroids with Dexamethasone

Axicabtagene Ciloleucel BIOLOGICAL

Given as standard of care

Also known as: Axi-cel, AXICABTAGENE CILOLEUCEL

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone; Prophylactic corticosteroids with Dexamethasone

Brexucabtagene Autoleucel BIOLOGICAL

Given as standard of care

Also known as: Brexu-cel, Anti-CD19 Autologous CAR-CD28 T-cells KTE-X19,

Hydrocortisone + Cytarabine + Dexamethasone or Methylprednisolone; Prophylactic corticosteroids with Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Histologically confirmed non-Hodgkin Lymphoma, including the following types defined by the World Health Organization (2017) or International Consensus Classification (2022):
• Diffuse large B-cell lymphoma (DLBCL)
• Primary mediastinal large B-cell lymphoma (PMBCL)
• Transformed follicular lymphoma (tFL)
• Transformed marginal zone lymphoma (tMZL)
• High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements
• Follicular lymphoma
• Mantle cell lymphoma
• Marginal zone lymphoma
• Meets institutional eligibility criteria to receive standard of care CD19 CAR T therapy.
• The participant (or legally acceptable representative if applicable) has provided documented informed consent for the trial.
• Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to allocation.
• Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests, including HBsAg and anti-HBc, are required for all participants.
• Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.

You may not qualify if:

• Patients with uncontrolled systemic infection despite appropriate antibiotics or other treatment.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• History of platelet transfusion refractoriness or participant declining transfusion support (i.e. Jehovah's witness).
• Participant requiring anti-platelets (aspirin, clopidogrel, ticagrelor) or systemic anticoagulants (coumadin, DOACs) which cannot be safely held at start of LD chemotherapy through Day+28. This is required to avoid delays in rapidly getting IT therapy.
• Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than high-grade B cell lymphoma. The only exceptions allowed are:
• Prior or concurrent indolent B cell lymphoma (follicular or marginal zone or lymphoplasmacytic lymphoma) with subsequent high-grade transformation
• Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured
• Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
• Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
• Localized prostate cancer (N0M0):
• With a Gleason score of ≤6, treated within the last 24 months, or untreated and under surveillance
• With a Gleason score of 3+4 that has been treated \>6 months prior to full study screening and considered to have a very low risk of recurrence; or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
• Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
• Other malignancy that is considered cured with minimal risk of recurrence.
• Known indolent bone marrow disorders such as monoclonal gammopathy of undetermined significance, clonal hematopoiesis of indeterminate potential that in the opinion of the Investigator or Sponsor do not present an increased risk of developing a secondary hematopoietic malignancy.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Gilead Sciences: collaborator

Study Sites (1)

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Recurrence

Interventions

Hydrocortisone; Cytarabine; Dexamethasone; Methylprednisolone; Cyclophosphamide; axicabtagene ciloleucel; brexucabtagene autoleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated; Prednisolone; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Bhagirathbhai Dholaria

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Services for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 13, 2026
• Study Start: September 25, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)