RecruitingPhase 2NCT06802315

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

Sponsor

University of Illinois at Chicago

Enrollment

38 participants

Start Date

Feb 4, 2025

Study Type

INTERVENTIONAL

Conditions

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

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

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria11

\. Age 18-65 years.
\. 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 Criteria11

\. Presence of significant co-morbidity as shown by:
a. Left ventricular ejection fraction \< 50%
b. Creatinine clearance \<30ml/min.
c. Bilirubin \> 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \> 5 x ULN.
d. FEV1 and FVC \< 50% of predicted or DLCO \<50% of predicted once corrected for anemia.
e. Karnofsky score \<70
f. Active viral hepatitis or HIV infection.
g. Cirrhosis.
\. Pregnancy or breast feeding
\. Patients unable to sign informed consent.
\. Patients previously received radiation to \>20% of bone marrow-containing areas.

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