NCT06802315

Intensity Modulated Total Marrow Irradiation in Fully Human Leukocyte Antigen (HLA)-Matched and Partially-HLA Mismatched Allogeneic Transplantation Patients With High-Risk Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), and Myelodysplastic Syndrome (MDS)

A Phase II Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Myeloablative Fludarabine/Busulfan and Post-Transplant Cyclophosphamide (PTCY) for Fully Human Leukocyte Antigen (HLA)-Matched and Partially-HLA Mismatched Allogeneic Transplantation Patients With High-Risk AML, CML, and MDS

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: University of Illinois at Chicago · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The study is a Phase II clinical trial. Patients will receive intensity-modulated total marrow irradiation (TMI) at a dose of 9 Gray (Gy) with standard myeloablative fludarabine intravenous (IV) and targeted busulfan (FluBu4) conditioning prior to allogeneic hematopoietic stem cell transplant (HSCT). Graft-versus-host disease (GVHD) prophylaxis will include Cyclophosphamide on Day +3 and +4, tacrolimus, and mycophenolate mofetil.

Detailed description

Patients will receive the following conditioning regimen: fludarabine 40 mg/m2 IV piggyback daily, from day -5 (5 days before stem cell infusion) through Day -2, IV busulfan targeting a 4800 μM/min/ day, from day -5 through day -2. In addition to the above chemotherapy, all patients will receive TMI at a dose of 3Gy on days -3, -2, and -1. On day 0, the stem cell product will be infused according to BMT (Bone Marrow Transplant) unit policy. Graft versus host disease (GVHD) prophylaxis will consist of the administration of Cyclophosphamide 50 mg/Kg on days 3 and 4 and mycophenolate mofetil combined with tacrolimus. Post-transplant evaluation will be done per standard care with study data collected at days 30, 60, 90, 180, 365, and 2 years.

Conditions

• Acute Myeloid Leukemia, Relapsed, Adult
• Acute Myeloid Leukemia Refractory
• Chronic Myeloid Leukemia - Accelerated Phase
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
RADIATION	Intensity modulated total marrow irradiation	See "Treatment Regimen"
DRUG	Cyclophosphamide (CTX)	This study will determine the safety of the combination of Total Marrow Irradiation (TMI) and Post-Transplant Cyclophosphamide using a myeloablative fludarabine and iv targeted busulfan (Flu/Bu4) conditioning regimen.
DRUG	Fludarabine (Fludara)	chemotherapy conditioning
DRUG	Busulfan (conditioning for ALLO Transplant)	chemotherapy conditioning

Timeline

• Start date: 2025-02-04
• Primary completion: 2030-03-01
• Completion: 2032-03-01
• First posted: 2025-01-31
• Last updated: 2025-06-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study