ImmunoMRI for Assessment of Tumor-associated Macrophages
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMedical University of Vienna
About this trial
About 35% of patients with a type of blood cancer called diffuse large B-cell lymphoma don't respond well to standard treatment or their cancer comes back. When this happens, newer treatments like CAR T-cell therapy (using modified immune cells) or bispecific antibodies (special proteins that help the immune system fight cancer) are an option. However, these treatments are only successful in about half the patients. It is currently difficult to predict which patients will respond to these treatments or experience serious side effects. This makes it hard to choose the best treatment plan for a given patient.
In this project, a special type of magnetic resonance imaging (MRI) scan will be used to track immune cells called macrophages that live around tumors. These cells can either help fight cancer or help cancer grow. By understanding how these cells behave, it may be possible to predict treatment success. The MRI technique involves injecting an iron-based substance called ferumoxytol, which can be used as an MRI contrast agent, into patients' veins. This contrast agent gets absorbed by the macrophages, making them visible on MRI scans throughout the entire body - not just one tumor spot. Sixty patients will be scanned before and after treatment (30 getting CAR T-cells, 30 getting bispecific antibodies), and results will be compared with tissue samples.
The goals are to predict which patients will go into complete remission, predict who will survive longer without cancer progression, and identify patients at risk for serious side effects like cytokine release syndrome. If successful, this imaging technique could help to personalize treatment choices, potentially improving outcomes while avoiding unnecessary toxicity in patients who will not benefit from these intensive therapies.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Pathology-proven relapsed/refractory DLBCL
Evidence of at least one anatomic site of tumor involvement on most recent prior imaging, e.g. CT, MRI, PET, or ultrasound, reflecting R/R DLBCL.
Ability to understand the study goals or outline and to give written informed consent.
Disqualifiers
Clinically confirmed pregnancy for women, or breast-feeding women; for pre-menopausal women who do not use hormonal contraception, a pregnancy test with a negative result will be required.
Age below the specified minimum of 18 years.
Any type of anemia at baseline (due to potentially altered ferumoxytol uptake)
Impaired renal function / renal insufficiency
Trial design
Design model
Single group
Treatments tested in this trial
MRI contrast-enhancing agents
Drug1. Ferumoxytol will be injected as an off-label MRI contrast agent at a dose of 4 mg/kg body mass. For safety (in accordance with prior research), ferumoxytol will be diluted 1:4 in saline, and administered slowly over at least 15 minutes, with patient monitoring during and post injection. 2. ImmunoMRI will be performed using an iron sensitive fat-suppressed, fast spoiled gradient echo T2\* mapping sequence. At each time point (i.e. pre-treatment and post-treatment), T2\* mapping will be performed before and \~24h after ferumoxytol injection.
Treatment groups
60 Participants
are divided into 1 treatment groupGroup A: Intravenous injection of ferumoxytol as off-label MRI contrast agent for tracking of macrophagesExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Correlation between immunoMRI and M1 and M2 TAM-directed IHC
To determine the associations between pre-treatment immunoMRI metrics and IHC-based TAM levels, median/mean T2\* will be calculated for each of the four IHC categories (score 1-4), separately for M1 and M2 TAMs, and Spearman rank correlation coefficients will be calculated.
Time frame
Through study completion, 3 years2
Prediction of complete remission (CR)
Median/mean pre-treatment T2\* and on-treatment T2\* changes (relative to baseline), will be compared between patients achieving/not achieving complete remission (CR). Logistic regression analyses will be used to test combinations of pre-treatment T2\* and △T2\*, and respective SUV (standardized uptake values) and MTV (metabolic tumor volumes) on PET and VOL (morphologic volumes) on MRI
Time frame
Through study completion, 3 years3
Prediction of 1-year overall survival (OS)
Median/mean pre-treatment T2\* and on-treatment T2\* changes (relative to baseline) will be compared between patients achieving/not achieving 1-year OS. Logistic regression analyses will be used to test combinations of pre-treatment T2\* and △T2\*, and respective SUV (standardized uptake values) and MTV (metabolic tumor volumes) on PET and VOL (morphologic volumes) on MRI, to predict 1-year OS.
Time frame
Through study completion, 3 years4
Prediction of 1-year PFS
Median/mean pre-treatment T2\* and on-treatment T2\* changes (relative to baseline) will be compared between patients achieving/not achieving 1-year OS. Logistic regression analyses will be used to test combinations of pre-treatment T2\* and △T2\*, and respective SUV (standardized uptake values) and MTV (metabolic tumor volumes) on PET and VOL (morphologic volumes) on MRI, to predict 1-year OS.
Time frame
Through study completion, 3 yearsSecondary outcomes
1
Correlation between post-treatment immunoMRI changes with changes in metabolic tumor activity and tumor size
To determine the association between early post-treatment changes in TAM levels and standard image-based tumor response, △T2\* (post-treatment T2\* - pretreatment T2\*) will be correlated with respective △SUVs, △MTV, and △VOL, using Pearson and Spearman correlation coefficients, as appropriate.
Time frame
Through study completion, 3 years2
Differences between males and females in terms of imaging metrics
Comparison of T2\* values between males and females
Time frame
Through study completion, 3 years3
Differences between males and females in terms of IHC scores
Comparison of TAM IHC scores between males and females
Time frame
Through study completion, 3 years4
Differences between males and females in terms of treatment response
Comparison of percentages of males and females achieving complete remission (CR)
Time frame
Through study completion, 3 yearsSponsors and contacts
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Source ClinicalTrials.gov
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