Proton-Based Total Marrow Irradiation for Allogeneic Transplantation in High-Risk AML/MDS

NCT07532824 | Recruiting Phase 1 DMC

• 1 other identifier: UHKT-PTC-TMI-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, single-center, non-randomized phase I/II pilot study evaluating proton-based Total Marrow Irradiation (TMI) as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients with high-risk or relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). These patients have an unfavorable prognosis with standard conditioning approaches. Participants will receive a standard conditioning regimen consisting of either myeloablative or reduced-intensity chemotherapy, selected according to age and comorbidities, combined with proton TMI delivered at a total dose of 12 Gy in three fractions. Graft-versus-host disease (GvHD) prophylaxis will be administered according to institutional standards, preferentially using post-transplant cyclophosphamide. Patients will subsequently undergo standard allo-HSCT and will be followed for at least 24 months after transplantation. The primary objective of the study is to assess the safety and tolerability of proton TMI added to standard conditioning, as measured by non-relapse mortality and treatment-related toxicity within the first 100 days after transplantation. Secondary objectives include evaluation of engraftment kinetics, incidence of relapse, overall and relapse-free survival, GvHD outcomes, and quality of life. Study outcomes will be analyzed descriptively and compared with a matched historical cohort.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)/AML; Proton Therapy; MDS and AML Prior to Allogeneic SCT; Myelodysplastic Neoplasm

Keywords

High-Risk Hematologic Malignancy; Total Marrow Irradiation; TMI; Proton Therapy; Conditioning Regimen; Targeted Radiotherapy; HSCT

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Incidence of treatment-related adverse events and serious adverse events occurring after conditioning including proton total marrow irradiation (TMI) added to standard conditioning prior to allogeneic hematopoietic stem cell transplantation; Incidence of Grade ≥3 adverse events according to CTCAE v5.0. Unit of Measure: Number of participants with at least one adverse event

  Up to 100 days post-transplantation

• Non-relapse mortality (NRM)

  Proportion of participants who die without prior disease relapse following allogeneic hematopoietic stem cell transplantation after conditioning including proton total marrow irradiation (TMI). Unit of Measure: Percentage of participants

  Up to 100 days post-transplantation

Secondary Outcomes (16)

• Cumulative incidence of neutrophil engraftment

  Up to 100 days post-transplantation

• Cumulative incidence of platelet engraftment

  Up to 100 days post-transplantation

• Transfusion independence

  Up to 100 days post-transplantation

• Incidence of primary graft failure

  Up to 100 days post-transplantation

• Cumulative incidence of relapse at 12 months

  12 months post-transplantation

Study Arms (1)

Proton TMI Conditioning Regimen

EXPERIMENTAL

Participants receive proton total marrow irradiation (TMI) added to a standard chemotherapy-based conditioning regimen prior to allogeneic hematopoietic stem cell transplantation.

Radiation: Proton Total Marrow Irradiation

Interventions

Proton Total Marrow Irradiation RADIATION

Proton total marrow irradiation (TMI) is administered as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation. TMI is delivered to a total dose of 12 cobalt gray equivalents (CGE) in 3 fractions of 4 CGE once daily. In patients with extramedullary disease or central nervous system involvement, additional site-specific irradiation may be administered prior to TMI (10 CGE in 5 fractions), with a simultaneous integrated boost to involved sites during TMI (3 fractions of 3.5 CGE). TMI is combined with standard chemotherapy-based conditioning regimens, including a myeloablative regimen (fludarabine, busulfan, post-transplant cyclophosphamide) or a reduced-intensity regimen (fludarabine, melphalan, post-transplant cyclophosphamide), according to institutional standards.

Proton TMI Conditioning Regimen

Eligibility Criteria

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

You may qualify if:

• Underlying diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS),
• A) Acute Myeloid Leukemia (AML), meeting at least one of the following criteria:
• i. Relapsed disease after a prior complete remission (CR) or
• ii. Disease refractory to at least two cycles of intensive chemotherapy or
• iii. High-risk AML in complete remission (CR), defined by at least one of the following:
• iii a) Adverse molecular or cytogenetic risk according to ELN 2022 classification or
• iii b) Presence of measurable/minimal residual disease (MRD).
• B) Myelodysplastic Syndrome (MDS), meeting at least one of the following criteria:
• i. Relapsed MDS with increased blasts (MDS-IB) or
• ii. MDS-IB2 without reduction of bone marrow blasts below 10% after induction chemotherapy or after at least two cycles of azacitidine or
• iii. IPSS-M score \> 0.5 (high-risk or very high-risk disease).
• Eligibility confirmed by the institutionalal Transplant Indication Committee according to standard criteria.
• Age ≥ 18 years and ≤ 65 years
• Ability to understand and voluntarily sign written informed consent

You may not qualify if:

• Severe comorbidity, defined as the presence of one or more of the following conditions:
• Left ventricular ejection fraction (LVEF) \< 40%
• Creatinine clearance \< 0.5 mL/s
• Total bilirubin \> 40 µmol/L (unless attributable to Gilbert's syndrome or hemolysis) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN)
• Pulmonary function impairment defined as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) \< 50% of predicted value, or diffusing capacity of the lung for carbon monoxide (DLCO) \< 50% of predicted value after correction for anemia
• Karnofsky Performance Status \< 70%
• Active viral hepatitis or human immunodeficiency virus (HIV) infection
• Presence of liver cirrhosis
• Pregnancy

Sponsors & Collaborators

• Institute of Hematology and Blood Transfusion, Czech Republic: lead
• Proton Therapy Center Czech s.r.o.: collaborator

Study Sites (2)

Institute of Hematology and Blood Transfusion

Prague, 12800, Czechia

RECRUITING

Proton Therapy Center Czech

Prague, 18000, Czechia

RECRUITING

Related Publications (17)

• The EBMT Handbook Textbook Open Access 2024

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Refractory; Anemia

Central Study Contacts

Veronika Valkova, Assoc. Prof., MD, PhD

CONTACT

+420 221 977 301; Veronika.Valkova@uhkt.cz

Jan Vydra, MD, PhD.

CONTACT

+420 221 977 290; Jan.Vydra@uhkt.cz

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants receive proton total marrow irradiation (TMI) added to standard pre-transplant conditioning prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). This open-label, non-randomized pilot study evaluates safety and tolerability of proton TMI in high-risk acute myeloid leukemia or myelodysplastic syndrome. No control group is used. Participants are followed throughout conditioning, transplantation, and post-transplant period to monitor engraftment, relapse, survival, graft-versus-host disease, and treatment-related adverse events.

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: April 16, 2026
• Study Start: November 21, 2025
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2)