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Hematological DiseaseAuToMINCT04976205

AI Algorithms to Automate the TMI by VMAT Optimization Using WB-CT/MRI and Synthetic WB-CT - The AuToMI Project

A study testing Total Marrow (Lymph-node) Irradiation in people with Hematological Disease, run by Istituto Clinico Humanitas at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Total Body Irradiation (TBI) was shown to help in providing immunosuppression that facilitates the donor transplant acceptance. Randomized trials demonstrated that conditioning regimens to bone marrow transplantation (BMT) including TBI have produced better survival rates than chemo-only regimens. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematological Disease
What is being tested?
Total Marrow (Lymph-node) Irradiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteItaly
Study dates
15 Jun 2021to 8 Aug 2025
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

  • Written, signed informed consent
  • Adult patients aged ≥18 years
  • Diagnosis of Hematological disease
  • Eligibility for allogeneic stem cell transplantation as center guidelines
  • TMI/TLI as part of the conditioning regimen

Who cannot join

  • Conditioning regimen including only chemotherapeutic agents

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • IRCCS Humanitas Research Center

    Rozzano, Milano, 20089

Other trials in Italy

About this study

Official title: Artificial Intelligence Algorithms to Automate the Total Marrow (Lymph-node) Irradiation by VMAT Optimization Using WB-CT/MRI and Synthetic WB-CT - The AuToMI Project

Total Body Irradiation (TBI) was shown to help in providing immunosuppression that facilitates the donor transplant acceptance. Randomized trials demonstrated that conditioning regimens to bone marrow transplantation (BMT) including TBI have produced better survival rates than chemo-only regimens. The TBI target is represented by the whole BM, and eventually the whole lymphatic system, liver, spleen. The increased life expectancy revealed the occurrence of important toxicities because of full doses received by organs at risk (OARs) and this limited the use of TBI. Many groups have explored the possibility of sophisticated techniques for reducing the dose to healthy tissues while increasing the dose to the BM. These newer approaches aim to generate total marrow (lymph-node) irradiation (TMI/TMLI), sparing as much as possible non-skeletal and non-lymphoid structures.

Actually, the time required to optimize a TMI/TMLI plan is 10 days. Therefore, the simulation Computed Tomography (CT) is performed many days before the BMT. Furthermore, the lymph-nodes are defined only on CT images.

Read the detailed description

Total Body Irradiation (TBI) was shown to help in providing immunosuppression that facilitates the donor transplant acceptance. Moreover, TBI plays a role in the annihilation of malignant cells, and may also deplete normal hematopoietic stem cells, thus helping the donor marrow cells to repopulate the bone marrow (BM). Randomized trials demonstrated that conditioning regimens to BMT including TBI have produced better survival rates than chemo-only regimens.

The TBI target is represented by the whole BM, and eventually the whole lymphatic system, liver, spleen. Usually, a very simple geometry is adopted, with patient positioned on a dedicated couch at 3-4 meters away from the linear accelerator to fully cover the target with a single beam, avoiding field junctions.

The increased life expectancy revealed the occurrence of important toxicities because of full doses received by organs at risk (OARs) and this limited the use of TBI as stated by the 2018 ILGROG guidelines. Many groups have, therefore, explored the possibility of sophisticated techniques for reducing the dose to healthy tissues while increasing the dose to the BM. These newer approaches aim to generate total marrow (lymph-node) irradiation (TMI/TMLI), sparing as much as possible non-skeletal and non-lymphoid structures.

Preliminary clinical data on phase I/II trials support the use of TMI/TMLI as part of conditioning for BMT for relapsed-refractory acute leukemia patients and multiple myeloma. However, TMI/TMLI adoption is still very limited to few skilled hospitals due to the extreme difficulty in the planning that needs many days.

The evaluation of TMI/TMLI with Volumetric Modulated Arc Therapy (VMAT) was started in our institute in 2009 and we treated around 90 patients in 10 years.

VMAT-TMI/TMLI requires multiple arcs from isocenters with different positions to fully include the patient length. Therefore, many field junctions between arcs with different isocenters should be managed. Furthermore, the CT length does not allow to acquire the patient in a single CT scan. Two CT series must be acquired and co-registered.

Actually, the time required to optimize a TMI/TMLI plan is 10 days. Therefore, the simulation Computed Tomography (CT) is performed many days before the BMT. Furthermore, the lymph-nodes are defined only on CT images.

Deep learning (DL) artificial intelligence (AI) algorithms in medical imaging and RT are rapidly expanding. DL focused on lesion detection and classification by features extraction. Image segmentations using fully convolutional network (FCN), holistically nested network (HNN) or other customized network architectures were implemented in many regions.

Over the past decades, the use of magnetic resonance imaging (MRI) to support RT has increased. MRI provides excellent soft-tissue imaging that could improve the target definition. The lymph-nodes contouring, based on MRI, will result in smaller target, enabling a better sparing of healthy tissues. Moreover, MRI significantly reduces inter/intra-observer contouring variability. At this aim, new generation MRI consoles with larger bore size, flat tabletops and dedicated imaging protocols with reduced image distortion to <1 mm were developed. Moreover, newly developed gradient-echo 3D sequences, and dedicated coils, can be used for producing a whole body WB-MRI acquisition in a few minutes. Furthermore, synthetic CT from MRI was proposed and implemented in some regions (i.e. brain and prostate) to substitute the CT for providing electron density information for dose planning calculation.

Being tested
Total Marrow (Lymph-node) Irradiation
Medical subject headings
Hematologic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Total Marrow (Lymph-node) IrradiationRadiation

    To the standard procedure for TMI/TMLI target definition, based on simulation WB-CT acquired 10/15 days before BMT, we acquire: WB- magnetic resonance imaging (MRI) the same day of the simulation WB-CT. A verification WB-CT will be performed 3/4 days before the delivery. Plans will be optimized with Volumetric Modulated Arc Therapy (VMAT) technique.

Study groups in NCT04976205
Study groupRoleWhat they receive
TMI/TMLIExperimentalThe standard planning optimization for TMI/TMLI preview a two-free-breathing-CT scan without contrast will be performed for simulation at day -15(-10) to the BMT. The same day a WB-MRI will be acquired for lymph-nodes delineation. WB-MRI scans will be performed using a 1.5T MR scanner. The two CT will be co-registered to the WB-MRI. CTV will be manually defined as the bones excluding mandible and hands (CTVBones), the spleen (CTVSpleen), and lymph nodes (CTVLN) using both MRI and CT images. The day -3 (4) to the BMT, further two-CT series will be acquired and co-registered to the first CTs for dose verification. Pre-treatment quality assurance (QA) will be performed the day before the treatment using the standard internal procedure. The treatment will be performed the day before the BMT.
Receives: Radiation: Total Marrow (Lymph-node) Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction of Lymph nodes target volume thanks to WB-MRI

    The PTV_LN volumes generated on the Simulation WB-MRI and on the Simulation WB-CT will be compared.

    Measured: 3 years

Secondary outcomes (1)
  1. Doses calcuated on CT performed at day -3 (4) to the BMT

    To evaluate the dosimetric changes that occurs in the days between the simulation and the delivery.

    The RT plan is defined on a simulation CT perfomed at -15 days. A second CT is performed at day -3 (4) to the BMT. The RT plan is recalculated on the second CT. The PTV volume receiving 95% of doses will be recorded.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2021
  2. Study start15 Jun 2021
  3. Primary completion8 Aug 2025
  4. Study completion8 Aug 2025

Resources

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
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04976205
Sponsor's protocol ID
2928
Acronym
AuToMI
Status last verified
Jan 2026
First submitted
30 Jun 2021
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Dei D, Lambri N, Sopranzi C, Galdieri C, Franzese C, Scorsetti M, Mancosu P. Impact of reduced interval from simulation CT to treatment delivery on dosimetric and positioning accuracy for total marrow lymph-node irradiation. Strahlenther Onkol. 2026 Mar;202(3):283-288. doi: 10.1007/s00066-025-02415-x. Epub 2025 Jun 13.

    PubMed 40512423

Questions about this trial

What is this clinical trial studying?

A study testing Total Marrow (Lymph-node) Irradiation in people with Hematological Disease, run by Istituto Clinico Humanitas at 1 site in Italy.

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 5 inclusion and 1 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 21 Jan 2026. 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 Italy. 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?

Reduction of Lymph nodes target volume thanks to WB-MRI (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04976205, which also lists 1 linked publication.

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 21 Jan 2026.

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