Safety and Feasibility of TMLI as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Radiation: total marrow and total lymphoid irradiation
- Registration Number
- NCT06209190
- Lead Sponsor
- Hospital Universitario Dr. Jose E. Gonzalez
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 14
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Total marrow and lymphoid irradiation (TMLI) total marrow and total lymphoid irradiation 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.
- Primary Outcome Measures
Name Time Method Early mortality rate 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 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).
- Secondary Outcome Measures
Name Time Method Measurable residual disease 60 days Measurable residual disease assessment through flow cytometry in bone marrow aspirate
Non-relapse mortality 12 months Event of death in patients without disease relapse with death after relapse as a competing risk.
Event-free survival 12 months Survival without event of disease progression, relapse or death after enrollment.
Overall survival 12 months Survival time after enrollment
Graft versus host disease incidence 12 months Incidence of graft versus host disease according to MAGIC and NIH criteria
Trial Locations
- Locations (1)
Andres Gomez
🇲🇽Monterrey, Nuevo LEON, Mexico