NCT07634536

Brief Summary

Intensive conditioning regimens used in allogeneic hematopoietic cell transplant (HCT) help to eliminate hematologic tumors and reduce the risk of relapse, but are also characterized by high toxicity. Total marrow and lymphoid irradiation (TMLI) is a specialized radiation technique that specifically targets marrow and lymphoid tissue to maximize antitumor efficacy while reducing off target toxicity. Despite these benefits, TMLI is technically challenging and time consuming. The radiation oncology team at Stanford has developed an automated TMLI platform to overcome these challenges. In this phase II trial, automation will be incorporated into a previously validated conditioning regimen of fludarabine/cyclophosphamide/TMLI HCT with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis to confirm the feasibility and safety of automation in patients receiving allogeneic HCT for high-risk myeloid malignancies.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
24mo left

Started Aug 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 4, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 9, 2026

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2026

Expected
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2028

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2028

Last Updated

June 9, 2026

Status Verified

June 1, 2026

Enrollment Period

2 years

First QC Date

June 4, 2026

Last Update Submit

June 4, 2026

Conditions

Acute Myeloid LeukemiaMyeloproliferative NeoplasmMyelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

  • Non-Relapse Mortality (NRM)

    Death without prior disease relapse following allogeneic peripheral blood stem cell transplantation.

    Day 100 after transplantation

  • Neutrophil Engraftment

    Neutrophil engraftment following allogeneic peripheral blood stem cell transplantation.

    Through Day 100 after transplantation

Secondary Outcomes (6)

  • Risk of Relapse

    Day 100 post-transplant

  • Disease-Free Survival (DFS)

    Day 100 post-transplant

  • Overall Survival (OS)

    Day 100 post-transplant

  • Incidence of Grade II-IV Acute Graft-versus-Host Disease (GVHD)

    Day 100 post-transplant

  • Incidence of Grade III-IV Acute Graft-versus-Host Disease (GVHD)

    Day 100 post-transplant

  • +1 more secondary outcomes

Study Arms (2)

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen

EXPERIMENTAL

Participants receive fludarabine, cyclophosphamide, and TMLI 200 cGy BID conditioning followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Post-transplant GVHD prophylaxis includes cyclophosphamide, mycophenolate mofetil, and tacrolimus.

Radiation: VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)Drug: FludarabineDrug: CyclophosphamideBiological: Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)Drug: Mycophenolate mofetil (MMF)Drug: Tacrolimus

Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen

EXPERIMENTAL

Participants receive fludarabine, cyclophosphamide, and TMLI 150 cGy BID conditioning followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Post-transplant GVHD prophylaxis includes cyclophosphamide, mycophenolate mofetil, and tacrolimus.

Radiation: VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)Drug: FludarabineDrug: CyclophosphamideBiological: Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)Drug: Mycophenolate mofetil (MMF)Drug: Tacrolimus

Interventions

FludarabineDRUG

Fludarabine 25 mg/m² IV administered daily on Days -7 through -3.

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenCohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen
CyclophosphamideDRUG

Cyclophosphamide 14.5 mg/kg IV on Days -7 and -6 as part of conditioning and 50 mg/kg IV on Days +3 and +4 as post-transplant GVHD prophylaxis.

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenCohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen
Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)BIOLOGICAL

Allogeneic peripheral blood stem cell transplantation administered on Day 0.

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenCohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen
TacrolimusDRUG

Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenCohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen
VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)RADIATION

Patients receive VMAT-based TMLI with daily image-guided radiation therapy (IGRT) for treatment localization and verification prior to radiation delivery.

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenCohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen
Mycophenolate mofetil (MMF)DRUG

Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.

Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenCohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age, Performance Status, and Graft Criteria require all of the following bullet points:
  • Age 18 to 60 years (inclusive)
  • HCT Co-Morbidity score (HCT-CI) \< 5 (http://www.qxmd.com/calculate-online/hematology/hct-ci)(31)
  • Adequate performance status is defined as Karnofsky score ≥ 70%
  • Patients must be receiving an allogeneic peripheral blood stem cell graft
  • Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8/8 matched sibling donor, 8/8 matched unrelated donor, haploidentical related donor, or 7/8 mismatched unrelated donor.
  • Eligible Diseases (Any one of the following)
  • Acute Myeloid Leukemia (AML) Must have at least one of the following characteristics:
  • Blasts \>5% in the peripheral blood and/or bone marrow after \>2 prior lines of AML directed therapy, present during the trial screening window
  • Adverse plus risk by AlloHCT Refined ELN Criteria: defined as having complex cytogenetics, TP53 mutation, or MECOM rearrangement confirmed at any time point.(32)
  • Myelodysplastic syndrome Must have at least one of the following characteristics at the time of conditioning:
  • Blasts \>10% in the peripheral blood and/or bone marrow after \>1 prior line of therapy.
  • TP53 mutation confirmed at any time point
  • Myeloproliferative neoplasms (MPN) or MDS/MPN overlap. Must have at least one of the following characteristics:
  • Blasts \>10% in the peripheral blood and/or bone marrow during the trial screening window
  • +15 more criteria

You may not qualify if:

  • Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
  • Untreated active infection. Controlled or asymptomatic infections requiring continued antimicrobial therapy are permissible.
  • Active HIV infection, defined as HIV infection with detectable viral load
  • Active central nervous system malignancy
  • GVHD requiring systemic therapy including \> 0.25 mg/kg prednisone (or equivalent) or other systemic therapy for GVHD (e.g., tacrolimus, sirolimus, ruxolitinib, belumosodil, ibrutinib, axatilimab).
  • Any other medical or psychological condition that is deemed serious and unsafe for clinical trial participation.
  • Exposure to prior radiation that is deemed unsafe for clinical trial participation.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteMyeloproliferative DisordersMyelodysplastic Syndromes

Interventions

Lymphatic IrradiationfludarabineCyclophosphamideMycophenolic AcidTacrolimus

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Diseases

Intervention Hierarchy (Ancestors)

RadiotherapyTherapeuticsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsMacrolidesLactones

Study Officials

  • Hany Elmariah, MD

    Stanford University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Hany Elmariah

CONTACT

650-723-0822he3@stanford.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 4, 2026

First Posted

June 9, 2026

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

August 1, 2028

Last Updated

June 9, 2026

Record last verified: 2026-06

Locations

US(1)