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Recurrent Diffuse Large B-Cell LymphomaPhase 2NCT07892027

Natalizumab for the Prevention of ICANS in Patients With Recurrent or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma Receiving CAR T-Cell Therapy

A Phase 2 study testing Axicabtagene Ciloleucel, Biospecimen Collection and Brexucabtagene Autoleucel in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Mantle Cell Lymphoma, run by University of Michigan Rogel 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
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Trial summary

This phase II studies how well natalizumab works in preventing immune effector cell associated neurologic syndrome (ICANS) in patients with diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) that has come back after a period of improvement (recurrent) or that does not respond to treatment (refractory)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Axicabtagene Ciloleucel, Biospecimen Collection and Brexucabtagene Autoleucel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
1 Nov 2026to 1 May 2028
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

  • Patient must be ≥ 18 years of age at the time of signing informed consent (ICF)
  • Patient must understand and voluntarily sign the ICF prior to conduct of any study-related assessments or procedures
  • Patient must be willing to adhere to the study visit schedule and other protocol requirements
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Patient must be eligible per institutional criteria for therapy with commercial axicabtagene ciloleucel or brexucabtagene autoleucel for treatment of relapsed or refractory diffuse large B-cell lymphoma or mantle cell lymphoma
  • Per institutional protocol: Females and males of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months (female) or 4 months (males with female partners of reproductive potential) after the cyclophosphamide infusion. The two contraception methods can consist of two barrier methods or a barrier method plus a hormonal method. Female participants must agree to inform their male partners that they must use the methods of birth control required by the protocol. The use of intrauterine devices is excluded due to the risk of infection or bleeding

Who cannot join

  • Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate antibiotics or treatment
  • Patients with infections controlled on antibiotics are not excluded
  • Prior history or current infection with John Cunningham (JC) virus
  • Active hepatitis B or C (latent hepatitis B will not be excluded), or HIV. Entecavir prophylaxis can be used for latent hepatitis B. Patients' viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing at screening
  • Bilirubin: ≥ 2.0 x upper limit of normal (ULN), unless attributed to Gilbert's Syndrome or to the patient's primary malignancy
  • Aspartate aminotransferase (AST): ≥ 5 x ULN, alanine aminotransferase (ALT): ≥ 5 x ULN
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  • Active concurrent autoimmune disease requiring immunosuppressive therapy
  • Active central nervous system (CNS) lymphoma
  • Active clinically relevant central nervous system disease including but not limited to:
  • Seizures/epilepsy
  • Stroke within the past 12 months, or unstable neurologic deficits within the past 12 months
  • Cerebral edema
  • Aphasia
  • Severe brain injury
  • Cerebellar disease
  • Documented history of dementia by clinical diagnosis
  • Parkinson's disease
  • Psychosis
  • Pregnant or nursing females
  • History of or active progressive multifocal leukoencephalopathy (PML)
  • Prior history or active herpes encephalitis or meningitis infection
  • Current treatment with any other agents for prophylaxis of CRS or ICANS, including investigational agents. Use of antiseizure medications does not exclude patients
  • History of prior exposure to natalizumab due to risk of neutralizing antibody formation
  • History of hypersensitivity reaction to natalizumab or the formulation excipients
  • Consider adding: History of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study

Trial locations and contacts

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

Tracey Churay contact

1-800-865-1125

tchuray@med.umich.edu

United States1 site, 1 recruiting

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

    Tracey Churay, 800-865-1125, tchuray@med.umich.edu

    Monalisa Ghosh

    Recruiting

Other trials in United States

About this study

Official title: Phase II Trial of Natalizumab for Prevention of Immune Effector Cell Associated Neurologic Syndrome (ICANS) in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy for B-Cell Hematologic Malignancies

This phase II studies how well natalizumab works in preventing immune effector cell associated neurologic syndrome (ICANS) in patients with diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) that has come back after a period of improvement (recurrent) or that does not respond to treatment (refractory) receiving chimeric antigen receptor (CAR) T-cell therapy. A major complication of CAR T-cell therapy is ICANS. ICANS is inflammation of the brain or nerves. ICANS currently requires high-dose corticosteroid treatment which can inhibit CAR T-cell response. Natalizumab prevents immune cells from traveling from the blood to the fluid around the brain, which is a process thought to play a major role in CAR T-cell related brain injury. Natalizumab may be safe and effective in decreasing the frequency of severe ICANS in patients with DLBCL or MCL receiving CAR T-cell therapy.

Being tested
Axicabtagene Ciloleucel, Biospecimen Collection, Brexucabtagene Autoleucel, Computed Tomography, Cyclophosphamide
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell

What participants receive

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

  • Axicabtagene CiloleucelBiological

    Also called Axi-cel, Axicel, KTE C19, KTE-C19

    Given axicabtagene ciloleucel

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Brexucabtagene AutoleucelBiological

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

    Given brexucabtagene autoleucel

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET/CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • NatalizumabBiological

    Also called AN100226, Antegren, Anti-alph4 Integrin Monoclonal Antibody AN100226, Anti-VLA4

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT07892027
Study groupRoleWhat they receive
Supportive care (SOC conditioning & CAR-T, natalizumab)ExperimentalPatients receive SOC conditioning therapy consisting of fludarabine IV and cyclophosphamide IV on days -4 and -3. Patients then receive natalizumab IV over 1 hour on day -1, followed by SOC CAR T-cell therapy with axicabtagene ciloleucel or brexucabtagene autoleucel on day 0. Patients also undergo PET/CT and blood sample collection throughout the study.
Receives: Biological: Axicabtagene Ciloleucel; Procedure: Biospecimen Collection; Biological: Brexucabtagene Autoleucel; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Natalizumab; Procedure: Positron Emission Tomography

What is being measured

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

  1. Occurrence of chimeric antigen receptor therapy (CAR-T)-associated neurotoxicity (immune effector cell associated neurotoxicity syndrome [ICANS])

    Any grade per American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome (ASTCT) criteria. Will be considered binary and the rate will be defined as number of patients without ICANS of any grade divided by the number of evaluable patients. These rates will be reported along with the 95% exact binomial confidence interval.

    Measured: Up to CAR-T day +28

Secondary outcomes (5)

  1. Occurrence of severe CAR-T-associated neurotoxicity (ICANS of grade 3 or greater)

    Defined by ASTCT consensus criteria. Will be considered binary and the rate will be defined as number of patients with severe ICANS divided by the number of evaluable patients. These rates will be reported along with the 95% exact binomial confidence interval.

    Measured: Up to CAR-T day +28

  2. Occurrence of severe cytokine release syndrome (cytokine release syndrome [CRS] of grade 3 or greater)

    Defined by ASTCT consensus criteria. Will be considered binary, and the rate will be defined as number of patients with severe CRS divided by the number of evaluable patients. These rates will be reported along with the 95% exact binomial confidence interval.

    Measured: Up to CAR-T day +28

  3. Occurrence of adverse events related to natalizumab

    Treatment emergent adverse events will be tabulated, and the rate will be defined as number of patients with treatment emergent adverse events divided by the number of evaluable patients. These rates will be reported along with the 95% exact binomial confidence interval.

    Measured: Up to CAR-T day +28

  4. Occurrence of complete response or partial response

    Assessed per Lugano classification on day +60 positron emission tomography/computed tomography. Will be defined as number of patients with treatment emergent adverse events divided by the number of evaluable patients. These rates will be reported along with the 95% exact binomial confidence interval.

    Measured: At CAR-T day +60

  5. Occurrence of serious adverse events related to natalizumab

    Treatment emergent serious adverse events will be tabulated, and the rate will be defined as number of patients with treatment emergent adverse events divided by the number of evaluable patients. These rates will be reported along with the 95% exact binomial confidence interval.

    Measured: Up to CAR-T day +28

Timeline

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

  1. First posted23 Oct 2026
  2. Study start1 Nov 2026 (estimated)
  3. Primary completion1 May 2028 (estimated)
  4. Study completion1 May 2028 (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
Supportive care
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07892027
Sponsor's protocol ID
UMCC 2026.011
Other IDs
NCI-2026-05450, HUM00289351
Status last verified
Oct 2026
First submitted
17 Oct 2026
Last updated
23 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 Axicabtagene Ciloleucel, Biospecimen Collection and Brexucabtagene Autoleucel in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Mantle Cell Lymphoma, run by University of Michigan Rogel 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 6 inclusion and 25 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 23 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 Tracey Churay (1-800-865-1125, tchuray@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of chimeric antigen receptor therapy (CAR-T)-associated neurotoxicity (immune effector cell associated neurotoxicity syndrome [ICANS]) (time frame: Up to CAR-T day +28). 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 NCT07892027.

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 23 Oct 2026.

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