Proton total marrow irradiation before allogeneic transplant for high-risk AML or MDS

Proton Total Marrow Irradiation-Based Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

This trial tests whether adding proton-based total marrow irradiation to standard chemotherapy conditioning before allogeneic stem cell transplant can improve outcomes for adults with high-risk or relapsed/refractory AML or MDS.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Institute of Hematology and Blood Transfusion, Czech Republic (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, radiation, fludarabine
• Locations: 2 sites (Prague and 1 other locations)
• Trial ID: NCT07532824 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-center, non-randomized phase I/II pilot trial of proton-based total marrow irradiation (TMI) given as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation. Participants receive either myeloablative or reduced-intensity chemotherapy chosen based on age and comorbidities, combined with proton TMI delivered as 12 Gy in three fractions. Graft-versus-host disease prophylaxis is given per institutional standards, with post-transplant cyclophosphamide preferred. Patients proceed to standard allo-HSCT and are followed for at least 24 months to monitor toxicity, relapse, and survival outcomes.

Who should consider this trial

Good fit: Adults with high-risk, relapsed, or refractory AML or high-risk MDS who are eligible for allogeneic hematopoietic stem cell transplantation and meet the institution's transplant selection criteria.

Not a fit: Patients with low-risk disease, those who are not candidates for allo‑HSCT, or those unable to access proton therapy or travel to the trial center are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could better spare normal organs from radiation, reduce transplant-related toxicity, and lower relapse or non-relapse mortality after allo‑HSCT.

How similar studies have performed: Photon-based TMI and intensified conditioning regimens have shown feasibility and improved organ sparing in prior reports, but proton-based TMI is a newer approach with limited published clinical outcome data.

Eligibility criteria

Inclusion Criteria:

1. 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).
2. Eligibility confirmed by the institutionalal Transplant Indication Committee according to standard criteria.
3. Age ≥ 18 years and ≤ 65 years
4. Ability to understand and voluntarily sign written informed consent

Exclusion Criteria:

Severe comorbidity, defined as the presence of one or more of the following conditions:

1. Left ventricular ejection fraction (LVEF) \< 40%
2. Creatinine clearance \< 0.5 mL/s
3. 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)
4. 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
5. Karnofsky Performance Status \< 70%
6. Active viral hepatitis or human immunodeficiency virus (HIV) infection
7. Presence of liver cirrhosis
8. Pregnancy

Where this trial is running

Prague and 1 other locations

• Institute of Hematology and Blood Transfusion — Prague, Czechia (Recruiting)
• Proton Therapy Center Czech — Prague, Czechia (Recruiting)

Study contacts

• Study coordinator: Veronika Valkova, Assoc. Prof., MD, PhD

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndrome/AML; Proton Therapy; MDS and AML Prior to Allogeneic SCT; Myelodysplastic Neoplasm; High-Risk Hematologic Malignancy; Total Marrow Irradiation; TMI