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Non-hodgkin LymphomaPhase 2NCT07763210

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

A Phase 2 study testing Therapeutic Hydrocortisone, Cytarabine and Dexamethasone in people with Non-hodgkin Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Therapeutic Hydrocortisone, Cytarabine and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteUnited States
Study dates
25 Sep 2026to 1 Oct 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • Participants must have completed curative anti-viral therapy at least 4 weeks prior to allocation.
  • Hepatitis C screening tests are not required unless: Known history of HCV infection as mandated by local health authority or institutional requirement for CAR T
  • Participants with HIV are eligible if they meet ALL of the following criteria:
  • The CD4 count is ≥ 350 cells/µL at screening
  • The HIV viral load is below the detectable level as per locally available testing
  • Are on a stable ART regimen for at least 4 weeks prior to study entry with good compliance
  • Note: ART includes drugs, which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study).
  • HIV screening tests are not required unless: Known history of HIV infection as mandated by local health authority or institutional requirement for CAR T
  • Adequate organ function as defined in the following table. Specimens must be collected within 30 days of LD chemo.
  • Absolute neutrophil count (ANC) ≥500/µL a Platelets ≥25 000/µL a Hemoglobin ≥7 g/dL a Renal Creatinine OR Measured or calculated b creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN (except known case of Gilbert's) AST (SGOT) and ALT (SGPT) ≤ 5× ULN Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Participants Assigned Male Sex at Birth
  • If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Cytarabine: 1 month
  • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
  • Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
  • Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak.
  • Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
  • Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
  • Participants Assigned Female Sex at Birth
  • A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a person of childbearing potential (POCBP) OR
  • Is a POCBP and: Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 3 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Cytarabine: 1 month- The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed. Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section X. Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with IT therapy. Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.

Who cannot join

  • Active HBV/HCV infection. See Inclusion Criteria 7 (HBV) and 8 (HCV) for requirements.
  • 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:
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  • 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.
  • A POCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for participant to start receiving study medication.
  • Primary CNS lymphoma, post-transplant lymphoproliferative disorder (PTLD)
  • Any history of active CNS involvement with lymphoma. Previously treated secondary CNS disease allowed as long as confirmed disease control based on imaging and negative CSF cytology.
  • Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
  • Is currently enrolled on another interventional therapeutic clinical trial which may impact the safety and/or efficacy of CAR T therapy.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
  • Has active autoimmune disease on active therapy with systemic biologics and/or prednisone ≥ 20mg/day equivalent. Vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are allowed to enroll.
  • Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications.
  • Note: Tumor biopsy and placement of central venous access devices are not considered major surgery.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Vanderbilt-Ingram Services for Timely Access contact

800-811-8480

cip@vumc.org

United States1 site, 1 recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37203

    Vanderbilt-Ingram Service Services for Timely Access, 800-811-8480, cip@vumc.org

    Bhagirathbhai Dholaria

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Trial of Early Enhanced Interventions to Prevent ICANS After CD19 CAR T Therapy in Patients With Non-Hodgkin Lymphoma: Lazarus Trial

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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVE:

  1. Impact of IT therapy on CAR T toxicities. II. Adverse events from IT therapy. III. Feasibility of IT therapy. IV. Impact of IT therapy on standard of care (SOC) manage (CRS) and ICANS. V. Impact of IT therapy on disease outcomes. VI. Impact of IT therapy on participants quality of life (QoL)

OUTLINE:

Patients receive standard of care cyclophosphamide based chemotherapy on day -5 to -3 and receive CAR T on day 0. Patients with grade 1/2 ICANS receive hydrocortisone and cytarabine IT along with standard of care dexamethasone or methylprednisolone. Patients with persistent or recurrent grade 1/2 ICANS receive hydrocortisone and cytarabine IT > 48 hours after initial treatment and patients with ≥ grade 3 ICANS receive hydrocortisone and cytarabine IT > 24 hours since initial treatment. Treatment is given in the absence of disease progression or unacceptable toxicity for a maximum of 2 treatments. Additional standard of care therapies may given if no improvement in 48 hours of IT therapy for grade 2 or 24 hours of IT therapy for grade 3/4 ICANS after discussion with study team. Patients undergo lumbar puncture for cerebrospinal fluid (CSF) collection on study and blood sample collection throughout the study.

Being tested
Therapeutic Hydrocortisone, Cytarabine, Dexamethasone, Methylprednisolone, Cyclophosphamide
Keywords
relapsed, refractory
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Therapeutic HydrocortisoneDrug

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

    100 mg IT with onset of grade 1/2 ICANS

  • CytarabineDrug

    Also called ARA-cell, Beta-Cytosine Arabinoside

    100 mg IT with onset of grade 1/2 ICANS

  • DexamethasoneDrug

    IV 10mg

  • MethylprednisoloneDrug

    1g daily until adverse events resolves

  • CyclophosphamideDrug

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

    Given as standard of care

  • Axicabtagene CiloleucelBiological

    Also called Axi-cel, AXICABTAGENE CILOLEUCEL

    Given as standard of care

  • Brexucabtagene AutoleucelBiological

    Also called Brexu-cel, Anti-CD19 Autologous CAR-CD28 T-cells KTE-X19,

    Given as standard of care

Study groups in NCT07763210
Study groupRoleWhat they receive
Hydrocortisone + Cytarabine + Dexamethasone or MethylprednisoloneExperimentalDrugs will be given at onset of grade 1/2 ICANS after Axi-cel or Brexu-cel
Receives: Drug: Therapeutic Hydrocortisone; Drug: Cytarabine; Drug: Dexamethasone; Drug: Methylprednisolone; Drug: Cyclophosphamide; Biological: Axicabtagene Ciloleucel; Biological: Brexucabtagene Autoleucel
Prophylactic corticosteroids with DexamethasoneActive comparatorDrugs will be given at onset of grade 1/2 ICANS after Axi-cel or Brexu-cel
Receives: Drug: Dexamethasone; Drug: Cyclophosphamide; Biological: Axicabtagene Ciloleucel; Biological: Brexucabtagene Autoleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. Progression free survival

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

    Measured: 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)

  1. Impact of IT therapy on CAR T toxicities

    Incidence, grade, duration of CRS and ICANS

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

  2. Adverse events from IT therapy

    Incidence of AE resulting from IT therapy

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

  3. Feasibility of IT therapy

    total number of IT therapy cycles per participant

    Measured: time from onset of ICANS to administration of first IT therapy

  4. Impact of IT therapy on SOC management of CRS and ICANS

    Number of inpatient hospital days among planned outpatient CAR T infusions. Number and type of systemic therapies for ICANS beyond steroids and IT therapy

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

  5. Impact of IT therapy on disease outcome

    ORR/CR rates; non-relapse mortality; cumulative incidence of G3 or higher infections

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

  6. Impact of IT therapy on participants QOL

    Completion of FACT-G (Functional Assessment of Cancer Therapy - General), a 27-item questionnaire used to measure the quality of life in cancer patients. Not at all 0 A little bit 1 Somewhat 2 Quite a bit 3 Very much 4

    Measured: time from screening through Post treatment Day +90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2026
  2. Study start25 Sep 2026
  3. Primary completion1 Mar 2028 (estimated)
  4. Study completion1 Oct 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07763210
Sponsor's protocol ID
VICCCTT26-01
Status last verified
Sep 2026
First submitted
4 Aug 2026
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Therapeutic Hydrocortisone, Cytarabine and Dexamethasone in people with Non-hodgkin Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Vanderbilt-Ingram Services for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of IT therapy to reduce high-grade ICANS in participants who receive axi-cel in NHL compared to historical experience (time frame: From first IT therapy through 14 days from last IT therapy (Up to 3 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07763210.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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