It is a randomized phase 3 study comparing two conditioning regimens in children with Acute Myeloid Leukemia, AML, undergoing allogenic stem cell transplantation. The primary aim is to investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to IV-free, chronic non-limited GvHD-free, relapse free survival than a conditioning regimen combining three alkylating agents (BuCyMel)
The study is designed as an open-label randomized phase III, multicenter superiority trial comparing two conditioning regimens CloFluBu and BuCyMel in children with acute myeloid leukemia (AML) with per-protocol indications to allogeneic hematopoietic stem cell transplantation with a myeloablative conditioning. This study is composed of two parts - an interventional part that includes randomization, and an observational part. The interventional part is a phase III randomized, open label, multicenter parallel group trial comparing two conditioning regimens used in pediatric HCT: a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm) and a combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm). The observational part will prospectively register outcome measures of transplantation in patients not fulfilling criteria for participation in the interventional part of the study (due to lack of complete remission, lack of matched sibling or unrelated donor, who were not recruited to a national upfront protocol or who decline participation in randomization) but consenting to registration of the data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
a three alkylator combination of busulfan, cyclophosphamide and melphalan (BuCyMel, standard arm)
combination of clofarabine, fludarabine and busulfan in which two alkylators are replaced by antimetabolites (CloFluBu, experimental arm)
L'Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)
Brussels, Belgium
NOT_YET_RECRUITINGCliniques Universitaires Saint-Luc (CUSL)
Brussels, Belgium
NOT_YET_RECRUITINGDepartment of Pediatric Hematology, Oncology and SCT, Ghent University Hospital
Ghent, Belgium
NOT_YET_RECRUITINGUniversity Hospital Leuven
Leuven, Belgium
NOT_YET_RECRUITINGCentre Hospitalier Régional de la Citadelle (CHR)/CHU Liège
Liège, Belgium
NOT_YET_RECRUITINGPaediatric Stem Cell Transplant and Immune Deficiency, Department of Pediatric and Adolescent Medicine, Section 4072, Rigshospitalet University Hospital of Copenhagen
Copenhagen, Denmark
RECRUITINGDivision of Hematology, Oncology, and Stem Cell Transplantation, The New Children's Hospital, Helsinki University Hospital
Helsinki, Finland
RECRUITINGDepartment of Pediatrics and Adolescent Medicine, Hong King Children's Hospital
Hong Kong, Hong Kong
NOT_YET_RECRUITINGSchneider Children's Medical Center of Israel
Petah Tikva, Israel
NOT_YET_RECRUITINGVilnius University Hospital Santaros Klinikos Center for Pediatric Oncology and Hematology
Vilnius, Lithuania
NOT_YET_RECRUITING...and 7 more locations
2-year, acute grade III to IV-free, chronic non-limited GvH-free, relapse-free survival (GREF)
To investigate if a conditioning regimen containing one alkylator (Bu) combined with two antimetabolites (Clo and Flu) results in superior 2-year acute grade III to IV-free, chronic non-limited GvHD-free, relapse free survival (GRFS) than a conditioning regimen combining three alkylating agents (BuCyMel)
Time frame: 2 years
Neutrophil and platelet engraftment
time to engraftment after stem cells transplantation, in all patients
Time frame: 28 days post transplantation
Primary graft failure
The incidence of graft failure defined as neutrophil recovery by day +28 post transplantation
Time frame: +28 days post transplantation
Secondary graft failure
The incidence of secondary graft failure
Time frame: 2 years
Cumulative incidence of relapse
The incidence of cumulative incidence of relapse during the first two years after transplantation
Time frame: 2 years
The association between pre-HCT MRD and relapse
% of remaining leukemic cells in the last bone marrow sample taken before start of conditioning
Time frame: 2 years
Cumulative incidence of transplant-related mortality
The incidence of transplant-related mortality at 2 years
Time frame: 2 years
Disease-free survival
Disease-free survival at 2 years
Time frame: 2 years
Overall survival
Overall survival at 2 years
Time frame: 2 years
Immunological recovery
Immunological recovery of CD3+ and CD4+ cells in peripheral blood
Time frame: 2 years
Incidence of grade II-IV and III-IV acute GVHD
The incidence of acute GvHD
Time frame: +180 days post transplantation
Incidence of chronic GVHD
The incidence of cGVHD
Time frame: 2 years
Incidence of grade ≥ 3 toxicity Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease
The rates of grade ≥ 3 Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease
Time frame: + 100 days post transplantation
Incidence of grade ≥ 3 toxicity Engraftment Syndrome (ES)
The incidence of engraftment syndome
Time frame: 2 years
Incidence of grade ≥ 3 toxicity Transplant-associated thrombotic microangiopathy (TA-TMA)
The incidence of TA-TMA
Time frame: 2 years
Incidence of grade ≥ 3 toxicity Hemorrhagic Cystitis (HC)
The incidence of HC
Time frame: 2 years
Incidence of grade ≥ 3 infections
The incidence of grade ≥ 3 infections of bacterial, viral and fungal origin
Time frame: 2 years
Health-Related Quality of Life, HRQoL.
HRQoL will be measured at baseline and at certain intervals using the quality of life instrument EQ-5D-Y, (Youth)™which include 2 measurements, the descriptive scale ( i.g. the score 1 is no problems and 3 is a lot of problems) and the VAS scale( 1 is the worst health and 100 is the best health that day).
Time frame: 2 years
Transplant-associated hormonal and gonadal late effects
the date of spontaneous puberty, date of spontaneous menarche for female patients and mean testicular volume for male patients, use of hormonal replacement therapy and use of fertility preservation
Time frame: 2 years
Nutritional status
BMI in kg/m\^2 at baseline and post transplantation
Time frame: 2 years
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