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)

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.

Eligibility

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.

Conditions5

Locations1 site

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