Acute Lymphoblastic LeukemiaNCT06209190
Safety and Feasibility of TMLI as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation
A study testing total marrow and total lymphoid irradiation in people with Acute Lymphoblastic Leukemia, run by Hospital Universitario Dr. Jose E. Gonzalez at 1 site in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 45 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- total marrow and total lymphoid irradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteMexico
- Study dates
- 1 Sep 2023to 4 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- total marrow and total lymphoid irradiation
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
total marrow and total lymphoid irradiationRadiation
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: total marrow and total lymphoid irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early mortality rate
Primary outcome of safety will be determined by early mortality rate (before day +30) with an expected rate lower than 15%.
Measured: 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).
Measured: 30 days
Secondary outcomes (5)
Measurable residual disease
Measurable residual disease assessment through flow cytometry in bone marrow aspirate
Measured: 60 days
Non-relapse mortality
Event of death in patients without disease relapse with death after relapse as a competing risk.
Measured: 12 months
Event-free survival
Survival without event of disease progression, relapse or death after enrollment.
Measured: 12 months
Overall survival
Survival time after enrollment
Measured: 12 months
Graft versus host disease incidence
Incidence of graft versus host disease according to MAGIC and NIH criteria
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start1 Sep 2023
- Primary completion4 Dec 2024
- Study completion4 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario Dr. Jose E. Gonzalez
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Gomez Almaguer, Hospital Universitario Dr. Jose E. Gonzalez
- Investigators
- David R Gomez-Almaguer, MD, Study chair, Universidad Autonoma de Nuevo Leon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06209190
- Sponsor's protocol ID
- Safety TMLI in HSCT
- Status last verified
- Mar 2026
- First submitted
- 31 Aug 2023
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28087456
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of Total Marrow and Total Lymphoid Irradiation as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation
- ClinicalTrials.gov ID
- NCT06209190
- Acronym / sponsor ID
- Safety TMLI in HSCT
- Conditions
- Acute Lymphoblastic Leukemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Hospital Universitario Dr. Jose E. GonzalezUniversity, hospital or other
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 4 Dec 2024 (actual)
- Study completion
- 4 Dec 2024 (actual)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Total marrow and lymphoid irradiation (TMLI) | Experimental | Radiation: total marrow and total lymphoid irradiationTMLI 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. |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| total marrow and total lymphoid irradiationdoses 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 | Radiation | Total marrow and lymphoid irradiation (TMLI) |
Primary outcome
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%.
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).
5 secondary outcomes
Measurable residual disease
Time frame: 60 days
Non-relapse mortality
Time frame: 12 months
Event-free survival
Time frame: 12 months
Overall survival
Time frame: 12 months
Graft versus host disease incidence
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2026.
- Background: PubMed 28087456Stein 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David R Gomez-Almaguer, MD study chair
Universidad Autonoma de Nuevo Leon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing total marrow and total lymphoid irradiation in people with Acute Lymphoblastic Leukemia, run by Hospital Universitario Dr. Jose E. Gonzalez at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early mortality rate (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06209190, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.