ImmunoMRI for Assessment of Tumor-associated Macrophages

NCT07066436 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: KLP5104424
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

DLBCL - Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (5)

• 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.

  Through study completion, 3 years

• 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

  Through study completion, 3 years

• 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.

  Through study completion, 3 years

• 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.

  Through study completion, 3 years

• Prediction of development of treatment toxicities (CRS, ICANS)

  Median/mean pre-treatment T2\*pre and on-treatment △T2\* values will be compared between patients developing/not developing cytokine release syndrom (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), and ROC analyses will be performed for each treatment group

  Through study completion, 3 years

Secondary Outcomes (6)

• Correlation between post-treatment immunoMRI changes with changes in metabolic tumor activity and tumor size

  Through study completion, 3 years

• Differences between males and females in terms of imaging metrics

  Through study completion, 3 years

• Differences between males and females in terms of IHC scores

  Through study completion, 3 years

• Differences between males and females in terms of treatment response

  Through study completion, 3 years

• Differences between males and females in terms of 1-year OS

  Through study completion, 3 years

Study Arms (1)

Intravenous injection of ferumoxytol as off-label MRI contrast agent for tracking of macrophages

EXPERIMENTAL

ImmunoMRI for tracking of TAMs will be integrated into 18F-FDG-PET/MRI scans that are performed for routine clinical purposes -i.e., assessment of disease extent before, and response assessment after/on treatment- to minimize patient discomfort and improve compliance. ImmunoMRI will be based on an iron sensitive fat-suppressed, fast spoiled gradient echo T2\* mapping sequence, obtained before and after intravenous injection of the iron oxide nanoparticle ferumoxytol (commerical name: Feraheme). For each patient immunoMRI will be performed twice: before treatment, and 3-4 weeks after start of treatment (CAR T cells or bispecific antibodies).

Drug: MRI contrast-enhancing agents

Interventions

MRI contrast-enhancing agents DRUG

1. 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.

Intravenous injection of ferumoxytol as off-label MRI contrast agent for tracking of macrophages

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• Known contraindication to MRI (per MRI Safety Guidelines, or conditions such as claustrophobia)
• Known hypersensitivity to ferumoxytol or any of its components, or history of allergic reaction to any intravenous iron product.

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

Related Publications (5)

• Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.

  PMID: 28925994 BACKGROUND

• Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6.

  PMID: 35717989 BACKGROUND

• Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, Raffeld M, Feldman S, Lu L, Li YF, Ngo LT, Goy A, Feldman T, Spaner DE, Wang ML, Chen CC, Kranick SM, Nath A, Nathan DA, Morton KE, Toomey MA, Rosenberg SA. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015 Feb 20;33(6):540-9. doi: 10.1200/JCO.2014.56.2025. Epub 2014 Aug 25.

  PMID: 25154820 BACKGROUND

• Nguyen KL, Yoshida T, Kathuria-Prakash N, Zaki IH, Varallyay CG, Semple SI, Saouaf R, Rigsby CK, Stoumpos S, Whitehead KK, Griffin LM, Saloner D, Hope MD, Prince MR, Fogel MA, Schiebler ML, Roditi GH, Radjenovic A, Newby DE, Neuwelt EA, Bashir MR, Hu P, Finn JP. Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI. Radiology. 2019 Dec;293(3):554-564. doi: 10.1148/radiol.2019190477. Epub 2019 Oct 22.

  PMID: 31638489 BACKGROUND

• Aghighi M, Theruvath AJ, Pareek A, Pisani LL, Alford R, Muehe AM, Sethi TK, Holdsworth SJ, Hazard FK, Gratzinger D, Luna-Fineman S, Advani R, Spunt SL, Daldrup-Link HE. Magnetic Resonance Imaging of Tumor-Associated Macrophages: Clinical Translation. Clin Cancer Res. 2018 Sep 1;24(17):4110-4118. doi: 10.1158/1078-0432.CCR-18-0673. Epub 2018 May 15.

  PMID: 29764855 BACKGROUND

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Marius E Mayerhoefer, MD, PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marius E Mayerhoefer, MD, PhD

CONTACT

+436642046495, +16469615030; marius.mayerhoefer@meduniwien.ac.at

Lucian Beer, MD

CONTACT

+4314040048180; lucian.beer@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Principal Investigator

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 15, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)