Acute Lymphoblastic Leukemia
Conditions
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.
Interventions
RADIATIONtotal 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
Sponsors
Hospital Universitario Dr. Jose E. Gonzalez
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
16 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Mexico
Contacts
STUDY_CHAIRDavid R Gomez-Almaguer, MD
Universidad Autonoma de Nuevo Leon
Outcome results
None listed