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.
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
- Conditions the study is for
- Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Mantle Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- Axicabtagene Ciloleucel, Biospecimen Collection and Brexucabtagene Autoleucel
- Type of treatment
- Injection or infusion, Surgery or procedure
- 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
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.
United States1 site, 1 recruiting
- Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Tracey Churay, 800-865-1125, tchuray@med.umich.edu
Monalisa Ghosh
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.
- Conditions
- Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Mantle Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Mantle Cell Lymphoma
- 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 group | Role | What they receive |
|---|---|---|
| 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. 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.
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)
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
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
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
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
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.
- First posted23 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 May 2028 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Monalisa Ghosh, Principal investigator, University of Michigan Rogel Cancer Center
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