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)

NCT06802315 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2024-0865
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Total Marrow Irradiation; Stem Cell Transplant; Allogenic Transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

• Overall Survival

  2 Years Post-Stem Cell Transplant

• Time To Engraftment

  30 Days Post-Stem Cell Transplant

• Adverse Events

  30 Days Post-Stem Cell Transplant

• Adverse Events

  60 Days Post-Stem Cell Transplant

• Adverse Events

  90 Days Post-Stem Cell Transplant

Study Arms (1)

Treatment Regimen

EXPERIMENTAL

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 1. year: Follow up 2. year: Follow up

Radiation: Intensity modulated total marrow irradiation; Drug: Cyclophosphamide (CTX); Drug: Fludarabine (Fludara); Drug: Busulfan (conditioning for ALLO Transplant)

Interventions

Intensity modulated total marrow irradiation RADIATION

See "Treatment Regimen"

Treatment Regimen

Cyclophosphamide (CTX) DRUG

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.

Treatment Regimen

Fludarabine (Fludara) DRUG

chemotherapy conditioning

Treatment Regimen

Busulfan (conditioning for ALLO Transplant) DRUG

chemotherapy conditioning

Treatment Regimen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Leukemia, Myeloid, Accelerated Phase; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Busulfan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Matias Sanchez, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matias Sanchez, MD

CONTACT

(312) 413-4260; matiass@uic.edu

Marisol Vega, MPH

CONTACT

(312) 413-5035; vegam35@uic.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: January 31, 2025
• Study Start: February 4, 2025
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2032
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

US (1)