Clinical trial NCT06209190: Safety and Feasibility of TMLI as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation
Official title: Safety and Feasibility of Total Marrow and Total Lymphoid Irradiation as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Lymphoblastic Leukemia
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2024-01-17
Enrollment: 14
Sex: ALL
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Early mortality rate
timeFrame: 30 days
measure: Serious adverse events
timeFrame: 30 days
Secondary outcomes:
measure: Measurable residual disease
timeFrame: 60 days
measure: Non-relapse mortality
timeFrame: 12 months
measure: Event-free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Graft versus host disease incidence
timeFrame: 12 months
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Andres Gomez
state: Nuevo LEON
Study officials:
affiliation: Universidad Autonoma de Nuevo Leon
name: David R Gomez-Almaguer, MD
role: STUDY_CHAIR
References:
citation: 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.