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

NCT ID: NCT06209190

Last Updated: 2024-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-01

Study Completion Date

2024-08-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

total marrow and total lymphoid irradiation

Intervention Type 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

Interventions

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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

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Universitario Dr. Jose E. Gonzalez

OTHER

Sponsor Role lead

Responsible Party

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David Gomez Almaguer

Head of hematology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David R Gomez-Almaguer, MD

Role: STUDY_CHAIR

Universidad Autonoma de Nuevo Leon

Locations

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Andres Gomez

Monterrey, Nuevo León, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Andrés Gómez-De León, MD

Role: CONTACT

+52833338111

Perla R Colunga-Pedraza, MD

Role: CONTACT

+528116089404

Facility Contacts

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Andres Gomez

Role: primary

818470002

References

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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.

Reference Type BACKGROUND
PMID: 28087456 (View on PubMed)

Related Links

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Other Identifiers

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Safety TMLI in HSCT

Identifier Type: -

Identifier Source: org_study_id

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