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
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.
Arms & interventions
- RadiationIntensity modulated total marrow irradiation
See "Treatment Regimen"
- DrugCyclophosphamide (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.
- DrugFludarabine (Fludara)
chemotherapy conditioning
- DrugBusulfan (conditioning for ALLO Transplant)
chemotherapy conditioning
Outcome measures
Primary
GVHD-Free Relapse-Free Survival after Stem Cell Transplant
The 1-year GVHD- free relapse-free survival after HSCT (hematopoietic stem cell transplantation) conditioned with a 9Gy TMI in combination with FluBu4 and PTCY in patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), Myelodysplastic Syndrome (MDS) at high risk of relapse.
Time frame: 1 Year Post-Stem Cell Transplant
Secondary
Overall Survival
Time frame: 2 Years Post-Stem Cell Transplant
Time To Engraftment
Time frame: 30 Days Post-Stem Cell Transplant
Adverse Events
Time frame: 30 Days Post-Stem Cell Transplant
Adverse Events
Time frame: 60 Days Post-Stem Cell Transplant
Adverse Events
Time frame: 90 Days Post-Stem Cell Transplant
Adverse Events
Time frame: 180 Days Post-Stem Cell Transplant
Adverse Events
Time frame: 1 Year Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease
Time frame: 30 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease
Time frame: 60 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease
Time frame: 90 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease
Time frame: 180 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease
Time frame: 1 Year Post-Stem Cell Transplant
Incidence of Chronic Graft Versus Host Disease
Time frame: 180 Days Post-Stem Cell Transplant
Incidence of Chronic Graft Versus Host Disease
Time frame: 1 Year Post-Stem Cell Transplant
Transplant-Related Mortality
Time frame: 30 Days Post-Stem Cell Transplant
Transplant-Related Mortality
Time frame: 60 Days Post-Stem Cell Transplant
Transplant-Related Mortality
Time frame: 90 Days Post-Stem Cell Transplant
Transplant-Related Mortality
Time frame: 180 Days Post-Stem Cell Transplant
Transplant-Related Mortality
Time frame: 1 Year Post-Stem Cell Transplant
Eligibility criteria
Study locations (1)
University of Illinois Cancer Center
Chicago, Illinois, 60612