Lymphoma, B-CellMR-ICANSNCT05510596
Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome
A study testing Magnetic Resonance Imaging with contrast injection, Blood withdrawal and Neuropsychological tests in people with Lymphoma, B-Cell and Neurotoxicity, run by University Hospital, Montpellier at 1 site in France.
Trial summary
The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, B-Cell, Neurotoxicity
- What is being tested?
- Magnetic Resonance Imaging with contrast injection, Blood withdrawal and Neuropsychological tests
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 22 Sep 2022to 14 Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Subject aged from 18 years old
- Subject able to understand the nature, purpose and methodology of the study
- Subject with diffuse large B-cell lymphoma to be treated with axicabtagene ciloleucel, tisagenlecleucel or brexucabtagene autoleucel for their lymphoma.
Who cannot join
- Refusal to sign the informed consent
- Subject presenting a cerebral localization of his lymphoma
- Contraindication to the realization of an MRI (metallic foreign body, pace-maker, cochlear implants)
- Claustrophobic subject
- Subject with a neurodegenerative disease (Parkinson's, Alzheimer's...)
- Subject with psychiatric disorders such as psychosis, except for anxiety-depressive episodes
Show all 15Show fewer
- Subject with a systemic pathology with neurological manifestation
- Subject with a previous or evolving neurological pathology
- Subject with or with a history of severe head trauma (group 2 or 3 according to the Masters classification)
- Contraindication to the use of gadoline contrast products (severe renal insufficiency, liver transplantation, known or suspected hypersensitivity to the product)
- Pregnant or breastfeeding women
- Patient under tutelage
- Patient under curatorship
- Patient deprived of liberty
- Not a beneficiary of a social security system
Trial locations and contacts
1 site in 1 country.
France1 site
Neurology department, Montpellier University Hospital
Montpellier, Occitanie, 34295
About this study
Official title: Contribution of Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome
The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate.
The mechanisms behind this neurotoxicity are unclear.
Read more
Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier.
To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods.
Main objectives are to compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity and to Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment.
For this purpose, 25 subjects will be included (the investigators hypothesize 40% with treatment-induced neurological impairment).
Read the detailed description
The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate.
The mechanisms behind this neurotoxicity are unclear but may include :
- A "systemic" toxicity associated with the cytokine release syndrome. This toxicity would thus be favoured by the associated inflammatory response syndrome manifested in particular by hyperthermia, changes in blood pressure, and an increase in CRP, ferritin and the number of white blood cells.
- A breakdown of the blood-brain barrier, as evidenced by increased protein levels, cellularity and cytokine levels in the cerebrospinal fluid. Among other things, this rupture could be promoted by the synthesis of proinflammatory cytokines (IL6, TNF-alpha, IFN-gamma) that would promote endothelial activation.
- Direct toxicity to neurons and/or microglial cells.
Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier.
To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods.
Objectives:
Main:
- To Compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity.
Secondary:
- To Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment.
- To Correlate the values of the MRI parameters with the usual clinical and biological parameters known to be associated with the occurrence of neurotoxicity (at D0 and theoretical peak).
- To Correlate the values of the MRI parameters with the values (at D0 and at NADIR) of a panel of cytokines of interest (V-PLEX Neuroinflammation Panel Human 1 Kit, Meso Scale Discovery®).
- Conditions
- Lymphoma, B-Cell, Neurotoxicity
- Being tested
- Magnetic Resonance Imaging with contrast injection, Blood withdrawal, Neuropsychological tests
- Keywords
- Neurotoxicity, CAR-T CELLS, Immune cells associated neurotoxicity syndrome, Cytokine release syndrome
- Medical subject headings
- Lymphoma, B-Cell, Neurotoxicity Syndromes, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance Imaging with contrast injectionOther
Magnetic Resonance Imaging with contrast injection
Blood withdrawalOther
Blood withdrawal : serum, plasma, cytokine assay
Neuropsychological testsOther
Neuropsychological tests
| Study group | Role | What they receive |
|---|---|---|
| Patients with CAR-T Cell treatment | Other | Single arm All patient will undergo an MRI with contrast injection, a blood withdrawal and a neurological consultation with neuropsychological tests Receives: Other: Magnetic Resonance Imaging with contrast injection; Other: Blood withdrawal; Other: Neuropsychological tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study of tissue permeability evolution
Quantitative measurement of KTRANS (rate of contrast agent transfer from plasma to the extravascular extracellular space, reflecting capillary permeability).
(Time in second)
Measured: 10 days
Secondary outcomes (16)
Qualitative analysis of tissue signals
FLAIR hypersignals analysis by MRI (signal of a tissue superior to the signal of the surrounding tissues) (visual assessment)
Measured: 10 days
Qualitative analysis
Microbleeding analysis (3DEPI T2*)
Measured: 10 days
Qualitative analysis
Analysis of contrast on injected 3DT1 MRI
Measured: 10 days
Semi-quantitative analysis of parameters associated with permeability
Wash-in, Wash-out (Time in second)
Measured: 10 days
Semi-quantitative analysis of parameters associated with permeability
Time to peak (TPP) (Time in second)
Measured: 10 days
Semi-quantitative analysis of parameters associated with permeability
AUC (area under the curve shows blood volume) (SI x Time)
Measured: 10 days
Quantitative analysis of parameters associated with permeability
Kep: rate of return transfer of the contrast agent from the extravascular extracellular space to the plasma (Volume/Time/Volume)
Measured: 10 days
Quantitative analysis of parameters associated with permeability
Ve: volume fraction of the extravascular space (Percentage %)
Measured: 10 days
Quantitative analysis of parameters associated with permeability
Vp: volume fraction of the plasma space. (Percentage %)
Measured: 10 days
Quantitative analysis
Cerebral blood flow analysis (3DPCASL) (L/min)
Measured: 10 days
Quantitative analysis
Cerebral volumetric analysis (3DT1) (cm3)
Measured: 10 days
Quantitative analysis
Diffusion coefficient (ADC) (mm²/s)
Measured: 10 days
Quantitative analysis
Perfusion factors (perfusion fraction f) (Percentage %)
Measured: 10 days
Quantitative analysis
Perfusion factors (pseudo-diffusion D* at the microvascular compartment) (x10^-3 mm²/s)
Measured: 10 days
Qualitative analysis : comparison with clinical data
Presence, absence of neurotoxicity and inflammation
Measured: 10 days
Comparison with biological data from standard care and "Neuroinflammation Panel Human 1 Kit"
Comparison of MRI data with biological markers (such as CRP, ferritin, white blood cell count, LDH, procalcitonin, fibrinogen) and cytokine profile of neuroinflammation by multiplex immunoassay kit. An ultrasensitive multiplex using electrochemiluminescence.
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2022
- Study start22 Sep 2022
- Primary completion13 Sep 2023
- Study completion14 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoma, B-CellStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Clarisse CARRA-DALLIERE, Dr, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05510596
- Sponsor's protocol ID
- RECHMPL20_0424
- Acronym
- MR-ICANS
- Status last verified
- Aug 2024
- First submitted
- 3 Jun 2022
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome
- ClinicalTrials.gov ID
- NCT05510596
- Acronym / sponsor ID
- MR-ICANS / RECHMPL20_0424
- Conditions
- Lymphoma, B-Cell, Neurotoxicity
- Keywords
- Neurotoxicity, CAR-T CELLS, Immune cells associated neurotoxicity syndrome, Cytokine release syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 22 Sep 2022 (actual)
- Primary completion
- 13 Sep 2023 (actual)
- Study completion
- 14 Sep 2023 (actual)
- First posted
- 22 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate.
The mechanisms behind this neurotoxicity are unclear.
Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier.
To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods.
Main objectives are to compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity and to Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment.
For this purpose, 25 subjects will be included (the investigators hypothesize 40% with treatment-induced neurological impairment).
Detailed description
The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate.
The mechanisms behind this neurotoxicity are unclear but may include :
- A "systemic" toxicity associated with the cytokine release syndrome. This toxicity would thus be favoured by the associated inflammatory response syndrome manifested in particular by hyperthermia, changes in blood pressure, and an increase in CRP, ferritin and the number of white blood cells.
- A breakdown of the blood-brain barrier, as evidenced by increased protein levels, cellularity and cytokine levels in the cerebrospinal fluid. Among other things, this rupture could be promoted by the synthesis of proinflammatory cytokines (IL6, TNF-alpha, IFN-gamma) that would promote endothelial activation.
- Direct toxicity to neurons and/or microglial cells.
Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier.
To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods.
Objectives:
Main:
- To Compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity.
Secondary:
- To Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment.
- To Correlate the values of the MRI parameters with the usual clinical and biological parameters known to be associated with the occurrence of neurotoxicity (at D0 and theoretical peak).
- To Correlate the values of the MRI parameters with the values (at D0 and at NADIR) of a panel of cytokines of interest (V-PLEX Neuroinflammation Panel Human 1 Kit, Meso Scale Discovery®).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with CAR-T Cell treatment | Other | Other: Magnetic Resonance Imaging with contrast injection, Other: Blood withdrawal, Other: Neuropsychological testsSingle arm All patient will undergo an MRI with contrast injection, a blood withdrawal and a neurological consultation with neuropsychological tests |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subject aged from 18 years old
- Subject able to understand the nature, purpose and methodology of the study
- Subject with diffuse large B-cell lymphoma to be treated with axicabtagene ciloleucel, tisagenlecleucel or brexucabtagene autoleucel for their lymphoma.
Key exclusion criteria (15 listed)
- Refusal to sign the informed consent
- Subject presenting a cerebral localization of his lymphoma
- Contraindication to the realization of an MRI (metallic foreign body, pace-maker, cochlear implants)
- Claustrophobic subject
- Subject with a neurodegenerative disease (Parkinson's, Alzheimer's...)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic Resonance Imaging with contrast injectionMagnetic Resonance Imaging with contrast injection | Other | Patients with CAR-T Cell treatment |
| Blood withdrawalBlood withdrawal : serum, plasma, cytokine assay | Other | Patients with CAR-T Cell treatment |
| Neuropsychological testsNeuropsychological tests | Other | Patients with CAR-T Cell treatment |
Primary outcome
Study of tissue permeability evolution
Time frame: 10 days
Quantitative measurement of KTRANS (rate of contrast agent transfer from plasma to the extravascular extracellular space, reflecting capillary permeability). (Time in second)
16 secondary outcomes
Qualitative analysis of tissue signals
Time frame: 10 days
Qualitative analysis
Time frame: 10 days
Qualitative analysis
Time frame: 10 days
Semi-quantitative analysis of parameters associated with permeability
Time frame: 10 days
Semi-quantitative analysis of parameters associated with permeability
Time frame: 10 days
Semi-quantitative analysis of parameters associated with permeability
Time frame: 10 days
Quantitative analysis of parameters associated with permeability
Time frame: 10 days
Quantitative analysis of parameters associated with permeability
Time frame: 10 days
Quantitative analysis of parameters associated with permeability
Time frame: 10 days
Quantitative analysis
Time frame: 10 days
Quantitative analysis
Time frame: 10 days
Quantitative analysis
Time frame: 10 days
Quantitative analysis
Time frame: 10 days
Quantitative analysis
Time frame: 10 days
Qualitative analysis : comparison with clinical data
Time frame: 10 days
Comparison with biological data from standard care and "Neuroinflammation Panel Human 1 Kit"
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clarisse CARRA-DALLIERE, Dr principal investigator
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magnetic Resonance Imaging with contrast injection, Blood withdrawal and Neuropsychological tests in people with Lymphoma, B-Cell and Neurotoxicity, run by University Hospital, Montpellier at 1 site in France.
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 3 inclusion and 15 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: finished, as of the sponsor's last update on 9 Aug 2024. 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 France. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study of tissue permeability evolution (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Aug 2024; AzTrials last refreshed its copy on 7 Nov 2026.