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

NCT07892027 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: UMCC 2026.011NCI-2026-05450HUM00289351
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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) 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.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (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.

  Up to CAR-T day +28

Secondary Outcomes (5)

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

  Up to CAR-T day +28

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

  Up to CAR-T day +28

• Occurrence of adverse events related to natalizumab

  Up to CAR-T day +28

• Occurrence of complete response or partial response

  At CAR-T day +60

• Occurrence of serious adverse events related to natalizumab

  Up to CAR-T day +28

Study Arms (1)

Supportive care (SOC conditioning & CAR-T, natalizumab)

EXPERIMENTAL

Patients 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.

Biological: Axicabtagene Ciloleucel; Procedure: Biospecimen Collection; Biological: Brexucabtagene Autoleucel; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Natalizumab; Procedure: Positron Emission Tomography

Interventions

Axicabtagene Ciloleucel BIOLOGICAL

Given axicabtagene ciloleucel

Also known as: Axi-cel, Axicel, KTE C19, KTE-C19, KTE-C19 CAR, KTEC19, Yescarta

Supportive care (SOC conditioning & CAR-T, natalizumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Supportive care (SOC conditioning & CAR-T, natalizumab)

Brexucabtagene Autoleucel BIOLOGICAL

Given brexucabtagene autoleucel

Also known as: Anti-CD19 Autologous CAR-CD28 T-cells KTE-X19, Brexu-cel, KTE X19, KTE-X19, KTEX19, Tecartus

Supportive care (SOC conditioning & CAR-T, natalizumab)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Supportive care (SOC conditioning & CAR-T, natalizumab)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Frindovyx, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Supportive care (SOC conditioning & CAR-T, natalizumab)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Supportive care (SOC conditioning & CAR-T, natalizumab)

Natalizumab BIOLOGICAL

Given IV

Also known as: AN100226, Antegren, Anti-alph4 Integrin Monoclonal Antibody AN100226, Anti-VLA4, Tysabri

Supportive care (SOC conditioning & CAR-T, natalizumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Supportive care (SOC conditioning & CAR-T, natalizumab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell

Interventions

axicabtagene ciloleucel; Specimen Handling; brexucabtagene autoleucel; Cyclophosphamide; fludarabine; Natalizumab; monoclonal antibody AN100226; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Monalisa Ghosh

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tracey Churay

CONTACT

1-800-865-1125; tchuray@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2026
• First Posted: October 23, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)