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RECRUITING
NCT07532824
PHASE1/PHASE2

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

Sponsor: Institute of Hematology and Blood Transfusion, Czech Republic

View on ClinicalTrials.gov

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.

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

Key Details

Gender

All

Age Range

18 Years - 65 Years

Study Type

INTERVENTIONAL

Enrollment

16

Start Date

2025-11-21

Completion Date

2029-11

Last Updated

2026-04-16

Healthy Volunteers

No

Interventions

RADIATION

Proton Total Marrow Irradiation

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.

Locations (2)

Institute of Hematology and Blood Transfusion

Prague, Czechia

Proton Therapy Center Czech

Prague, Czechia