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)

Launched by UNIVERSITY OF ILLINOIS AT CHICAGO · Jan 28, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment approach for patients with high-risk blood cancers, specifically Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), and Myelodysplastic Syndrome (MDS). The treatment involves a method called intensity-modulated total marrow irradiation (TMI), which helps prepare the body for a stem cell transplant. This trial aims to see if this method can improve outcomes for patients who have had relapses or who are not responding to standard treatments.

To participate, patients need to be between 18 and 65 years old and have specific types of blood cancers that meet certain criteria, such as having relapsed AML or poor-risk MDS. Those with significant other health issues or who are pregnant cannot join. Participants will receive the TMI treatment and then undergo a stem cell transplant, along with medications to help prevent complications. The study is currently recruiting and aims to provide new options for patients facing challenging diagnoses.

Gender

ALL

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.