Safety and Feasibility of TMLI as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation

March 24, 2026 updated by: David Gomez Almaguer, Hospital Universitario Dr. Jose E. Gonzalez

Safety and Feasibility of Total Marrow and Total Lymphoid Irradiation as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation

Multiple conditioning regimens have been used for the HSCT, some of which include radiotherapy. Total body irradiation (TBI) has demonstrated to be superior to chemotherapy alone in the phase III FORUM trial. However, concerns for long-term toxicity have made TBI less used. Total marrow and lymphoid irradiation (TMLI) has emerged as a new alternative that can potentially keep the benefits of radiation but reducing toxicity to healthy tissues.

The primary objective of this trial is to evaluate the feasibility and safety of TMLI as part of conditioning schemes with or without etoposide for HSCT in patients between age 16 and 45 years with ALL in first line or relapsed disease. As secondary endpoint the efficacy will be assessed by minimal residual disease at 60 days post-transplant, as well as other outcome measures such as non-relapse mortality (NRM), relapse free survival (RFS) and overall survival (OS).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

TMLI will be administered as part of the conventional reduced intensity conditioning scheme of our institution:

Fludarabine 25 mg/m2 + cyclophosphamide 350 mg/m2 on days -6 to -3, for patients with positive measurable residual disease TMLI will be added in doses of 12 Gy on days -3 to -1 divided into 6 fractions of 2 Gy every 12 hours for 3 days, which will be administered through a computed tomography tomotherapy system.

Infusion of peripheral blood hematopoietic stem cells will be performed on day 0 and after this, prophylaxis for GVHD with post-transplant cyclophosphamide 50 mg/kg will be administered on days +3 and +4, followed by tacrolimus or cyclosporine A plus mycophenolate mofetil regardless of HLA matching.

The procedure for the donation of hematopoietic cells will be done through a peripheral blood apheresis with previous stimulation with filgrastim at 10 mcg/kg for 4 days according to the standardized procedures of our institution.

The leukocyte and platelet count will be monitored by serial complete blood count, and a bone marrow aspiration (BMA) and minimal residual disease (MRD) will be performed on day 60 after transplantation.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64710
        • Andres Gomez

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of ALL confirmed by flow cytometry.
  • Patients between age 16 and 45 years with ALL in first remission, refractory, or relapsing
  • Patients who have an identical or haploidentical allogeneic donor by high resolution HLA

Exclusion Criteria:

  • Patients who do not meet the age previously mentioned.
  • Patient with comorbidities that rule them out for HSCT, with a Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) greater than 2.
  • Poor performance status or Karnofsky less than 70%
  • Transthoracic echocardiogram with alteration in myocardial function with left ventricular ejection fraction (LVEF) less than 50%
  • Patients who previously and for another reason have already received radiotherapy or who refuse to receive it

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Total marrow and lymphoid irradiation (TMLI)
TMLI will be added in doses of 12 Gy on days -3 to -1 divided into 6 fractions of 2 Gy every 12 hours for 3 days, which will be administered through a computed tomography tomotherapy system.
Radiation: total marrow and total lymphoid irradiation
doses of 12 Gy on days -3 to -1 divided into 6 fractions of 2 Gy every 12 hours for 3 days, which will be administered through a computed tomography tomotherapy system plus conditioning scheme of our institution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Early mortality rate
Time Frame: 30 days
Primary outcome of safety will be determined by early mortality rate (before day +30) with an expected rate lower than 15%.
30 days
Serious adverse events
Time Frame: 30 days
Co-primary outcome will be the appearance of serious adverse effects (grade equal to or higher than 3) according to the common terminology criteria for adverse events of the US National Cancer Institute (NCL-CTCAE v.5).
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurable residual disease
Time Frame: 60 days
Measurable residual disease assessment through flow cytometry in bone marrow aspirate
60 days
Non-relapse mortality
Time Frame: 12 months
Event of death in patients without disease relapse with death after relapse as a competing risk.
12 months
Event-free survival
Time Frame: 12 months
Survival without event of disease progression, relapse or death after enrollment.
12 months
Overall survival
Time Frame: 12 months
Survival time after enrollment
12 months
Graft versus host disease incidence
Time Frame: 12 months
Incidence of graft versus host disease according to MAGIC and NIH criteria
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitario Dr. Jose E. Gonzalez

Investigators

  • Study Chair: David R Gomez-Almaguer, MD, Universidad Autonoma de Nuevo Leon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2023

Primary Completion (Actual)

December 4, 2024

Study Completion (Actual)

December 4, 2024

Study Registration Dates

First Submitted

August 31, 2023

First Submitted That Met QC Criteria

January 5, 2024

First Posted (Actual)

January 17, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Safety TMLI in HSCT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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