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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
Who can join
Ages 18 to 65 · All sexes
Full eligibility criteria
Inclusion Criteria: * 1\. Age 18-65 years. * 2\. Patients with CML, AML, or MDS who meet one of the following criteria: 2a. Relapsed or refractory AML (including AML in CR2) 2b. Poor-risk AML in first remission, with remission defined as \<5% bone marrow blasts morphologically: * AML arising from MDS, a myeloproliferative disorder, or secondary AML * Poor risk molecular features according to Leukemia Net including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 * Poor-risk cytogenetics: Monosomal karyotype, complex karyotype (\> 3 abnormalities), inv (3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7. 2c. Primary refractory disease 2d. MDS with at least one of the following poor-risk features: * Poor-risk cytogenetics including 3q abnormalities, 7/7q minus or complex cytogenetics (\>3 abnormalities). * Current or previous INT-2 or high IPSS score. * Treatment-related MDS. * MDS diagnosed before the age of 21 years. * Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy. * Life-threatening cytopenias, including those requiring regular PRBC or platelet transfusions. 2e. CML with a history of accelerated or blast phase. Exclusion Criteria: * 1\. Presence of significant co-morbidity as shown by: * 1a. Left ventricular ejection fraction \< 50% * 2b. Creatinine clearance \<30ml/min. * 3c. Bilirubin \> 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \> 5 x ULN. * 4d. FEV1 and FVC \< 50% of predicted or DLCO \<50% of predicted once corrected for anemia. * 5e. Karnofsky score \<70 * 6f. Active viral hepatitis or HIV infection. * 7g. Cirrhosis. * 2\. Pregnancy or breast feeding * 3\. Patients unable to sign informed consent. * 4\. Patients previously received radiation to \>20% of bone marrow-containing areas.
About the study
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.
What is being tested
- Intensity modulated total marrow irradiation (radiation)
- Cyclophosphamide (CTX) (drug)
- Fludarabine (Fludara) (drug)
- Busulfan (conditioning for ALLO Transplant) (drug)
Sponsor: University of Illinois at Chicago · Participants: 38 · Started: Feb 4, 2025
Contact the study team
- Matias Sanchez, MD · Phone: (312) 413-4260
- Marisol Vega, MPH · Phone: (312) 413-5035
Official record on ClinicalTrials.gov — NCT06802315
Locations in the U.S.
| Illinois | University of Illinois Cancer Center, Chicago |
Conditions
From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.