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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06209190
• Other study ID #: Safety TMLI in HSCT
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: January 2024
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: Andrés Gómez-De León, MD
• Phone: +52833338111
• Email: drgomezdeleon[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: August 31, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
Mexico	Andres Gomez	Monterrey	Nuevo LEON

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & 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. — View Citation

Outcome

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

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