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

NCT06209190 | Completed DMC

• 1 other identifier: Safety TMLI in HSCT
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Early mortality rate

  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

  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 Outcomes (5)

• Measurable residual disease

  60 days

• Non-relapse mortality

  12 months

• Event-free survival

  12 months

• Overall survival

  12 months

• Graft versus host disease incidence

  12 months

Study Arms (1)

Total marrow and lymphoid irradiation (TMLI)

EXPERIMENTAL

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

Interventions

total marrow and total lymphoid irradiation RADIATION

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

Total marrow and lymphoid irradiation (TMLI)

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Universitario Dr. Jose E. Gonzalez: lead

Study Sites (1)

Andres Gomez

Monterrey, Nuevo León, 64710, Mexico

Location

Related Publications (1)

• Stein A, Palmer J, Tsai NC, Al Malki MM, Aldoss I, Ali H, Aribi A, Farol L, Karanes C, Khaled S, Liu A, O'Donnell M, Parker P, Pawlowska A, Pullarkat V, Radany E, Rosenthal J, Sahebi F, Salhotra A, Sanchez JF, Schultheiss T, Spielberger R, Thomas SH, Snyder D, Nakamura R, Marcucci G, Forman SJ, Wong J. Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia. Biol Blood Marrow Transplant. 2017 Apr;23(4):618-624. doi: 10.1016/j.bbmt.2017.01.067. Epub 2017 Jan 10.

  PMID: 28087456 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• David R Gomez-Almaguer, MD

  Universidad Autonoma de Nuevo Leon

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of hematology

Model Details: Our study will enroll 14 patients in an estimated period of 2 years, with non-probabilistic sampling based on consecutive cases from January 2022 to January 2024 based on prior local transplant data. The study will be done according with the Declaration of Helsinki, and with Good Clinical Practice guidelines and the protocol will be approved by local Institutional Review Board after external review and will be locally funded. Descriptive statistics will be used to report the baseline variables of the patients. Groups will be compared with hypothesis tests through deductive statistics using Student's t test or Mann Whitney U test accordingly, to determine significant differences between two groups and their means; and the Chi square test as a verification test and comparison of hypotheses of categorical data, in addition, survival analysis will be carried out by the Kaplan-Meier method and competing risk analysis as appropriate.

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: January 17, 2024
• Study Start: September 1, 2023
• Primary Completion: December 4, 2024
• Study Completion: December 4, 2024
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)