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) (BMT-13)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia Refractory; Chronic Myeloid Leukemia - Accelerated Phase; Acute Myeloid Leukemia, Relapsed, Adult
• Intervention / Treatment: Radiation: Intensity modulated total marrow irradiation; Drug: Cyclophosphamide (CTX); Drug: Fludarabine (Fludara); Drug: Busulfan (conditioning for ALLO Transplant)

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.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Matias Sanchez, MD; Phone Number: (312) 413-4260; Email: matiass@uic.edu
• Study Contact Backup: Name: Marisol Vega, MPH; Phone Number: (312) 413-5035; Email: vegam35@uic.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
      • Contact: Marisol Vega, MPH; Phone Number: (312) 413-5035; Email: vegam35@uic.edu
      • Contact: Matias Sanchez, MD; Phone Number: 312-413-4260; Email: matiass@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Regimen; Days -5 through -2: Fludarabine 40 mg/m2 IVPB daily and Busulfan targeting AUC 4800μM/min daily Day -3 through -1: Intensity modulated total marrow irradiation (9Gy fractionated) Day 0: Infuse peripheral blood mobilized stem cells Days +3 and +4: Cyclophosphamide 50 mg/kg/day Day 5: Mycophenolate mofetil and Tacrolimus (dose adjustment dependent on trough level) Day 30: Follow up Day 60: Follow up Day 90: Follow up Day 180: Follow up; year: Follow up; year: Follow up

Radiation: Intensity modulated total marrow irradiation; See "Treatment Regimen"; Drug: Cyclophosphamide (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.; Drug: Fludarabine (Fludara); chemotherapy conditioning; Drug: Busulfan (conditioning for ALLO Transplant); chemotherapy conditioning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 Year Post-Stem Cell Transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The number of participants who have overall survival	2 Years Post-Stem Cell Transplant
Time To Engraftment		30 Days Post-Stem Cell Transplant
Adverse Events	The number of adverse events and grades of severity per Common Terminology of Criteria for Adverse Events (version 5.0) and the Bearman scale.	30 Days Post-Stem Cell Transplant
Adverse Events	The number of adverse events and grades of severity per Common Terminology of Criteria for Adverse Events (version 5.0).	60 Days Post-Stem Cell Transplant
Adverse Events	The number of adverse events and grades of severity per Common Terminology of Criteria for Adverse Events (version 5.0)	90 Days Post-Stem Cell Transplant
Adverse Events	The number of adverse events and grades of severity per Common Terminology of Criteria for Adverse Events (version 5.0).	180 Days Post-Stem Cell Transplant
Adverse Events	The number of adverse events and grades of severity per Common Terminology of Criteria for Adverse Events (version 5.0).	1 Year Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease	The number of participants with Acute Graft Versus Host Disease	30 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease	The number of participants with Acute Graft Versus Host Disease	60 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease	The number of participants with Acute Graft Versus Host Disease	90 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease	The number of participants with Acute Graft Versus Host Disease	180 Days Post-Stem Cell Transplant
Incidence of Acute Graft Versus Host Disease	The number of participants with Acute Graft Versus Host Disease	1 Year Post-Stem Cell Transplant
Incidence of Chronic Graft Versus Host Disease	The number of participants with Chronic Graft Versus Host Disease	180 Days Post-Stem Cell Transplant
Incidence of Chronic Graft Versus Host Disease	The number of participants with Chronic Graft Versus Host Disease	1 Year Post-Stem Cell Transplant
Transplant-Related Mortality	The number of participants with transplant-related mortality	30 Days Post-Stem Cell Transplant
Transplant-Related Mortality	The number of participants with transplant-related mortality	60 Days Post-Stem Cell Transplant
Transplant-Related Mortality	The number of participants with transplant-related mortality	90 Days Post-Stem Cell Transplant
Transplant-Related Mortality	The number of participants with transplant-related mortality	180 Days Post-Stem Cell Transplant
Transplant-Related Mortality	The number of participants with transplant-related mortality	1 Year Post-Stem Cell Transplant

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Matias Sanchez, MD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2032

Study Registration Dates

• First Submitted: January 28, 2025
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): January 31, 2025

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Stem Cell Transplant; Total Marrow Irradiation; Allogenic Transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Myeloproliferative Disorders; Syndrome; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Busulfan
• Other Study ID Numbers: 2024-0865

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No