Recruiting
Phase 2

Natalizumab

Sponsor:

University of Michigan Rogel Cancer Center

Code:

NCT07892027

Conditions

Recurrent Diffuse Large B-Cell Lymphoma

Recurrent Mantle Cell Lymphoma

Refractory Diffuse Large B-Cell Lymphoma

Refractory Mantle Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Axicabtagene Ciloleucel

Biospecimen Collection

Brexucabtagene Autoleucel

Computed Tomography

Cyclophosphamide

Study Details

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

Study ID

NCT07892027

Start date

Nov 1, 2026

Status verified date

Oct, 2026

Completion date

May 1, 2028

Anticipated

Primary completion date

May 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Design

Enrollment

26 participants

Anticipated

Intervention Model

Single group

Primary purpose

Supportive Care

Interventions and Outcome Measures

Arms

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

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.

Interventions

Axicabtagene Ciloleucel

Given axicabtagene ciloleucel

Biospecimen Collection

Undergo collection of blood

Brexucabtagene Autoleucel

Given brexucabtagene autoleucel

Computed Tomography

Undergo PET/CT

Cyclophosphamide

Given IV

Fludarabine

Given IV

Natalizumab

Given IV

Positron Emission Tomography

Undergo PET/CT

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 ]

Central Contacts and Locations

Central contacts

Tracey Churay

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

Locations

University of Michigan Rogel Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Tracey Churay

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

Principal Investigator:

Monalisa Ghosh

More Information

Sponsor

University of Michigan Rogel Cancer Center

Last update posted

Oct 23, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by University of Michigan Rogel Cancer Center on 2026-10-23. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.